adenine and B-Cell Chronic Lymphocytic Leukemia studies

Research Excerpts

Excerpt	Relevance	Reference
"Moving from the recognition that infection control represents an unmet need, the Italian Society of Hematology (SIE) convened a panel of experts who had published and/or expressed an interest in infection complications in CLL."	6.61	Infection control in patients treated for chronic lymphocytic leukemia with ibrutinib or idelalisib: recommendations from Italian society of hematology. ( Barosi, G; Gaidano, G; Girmenia, C; Marchetti, M; Pane, F; Rambaldi, A; Tura, S; Zinzani, PL, 2019)
" He was diagnosed as having fibrinoid syndrome and started on topical prednisolone, brimonidine, timolol-dorzolamide, and orally administered acetazolamide."	4.98	Anterior chamber fibrinoid syndrome after cataract extraction in a patient on ibrutinib for B-cell chronic lymphocytic leukemia: a case report and review of the literature. ( Hwang, CK; Kim, BJ; Kolomeyer, AM, 2018)
" He was diagnosed with type I cryoglobulinemia and treated with rituximab, plasmapheresis, methylprednisolone, and ibrutinib was restarted."	3.91	Cryoglobulinemic vasculitis with interruption of ibrutinib therapy for chronic lymphocytic leukemia (CLL). ( Field, J; George, G; Singavi, A; Voshtina, E; Wright, N, 2019)
" Ibrutinib use, age, hypertension, and previous use of ACE inhibitors, angiotensin receptor blocker use, β blocker use, and aspirin use were independently associated with incident arrhythmias."	3.91	Rates and Risk of Atrial Arrhythmias in Patients Treated With Ibrutinib Compared With Cytotoxic Chemotherapy. ( Armanious, M; Chavez, JC; Emole, J; Fradley, MG; Gliksman, M; Lee, DH; McLeod, H; Pinilla-Ibarz, J; Rhea, I; Schabath, MB; Shah, B; Viganego, F; Walko, C; Welter-Frost, A, 2019)
" Ibrutinib dosing was held (≥7 days) for 79 patients and reduced for 31 patients because of AEs; these AEs resolved or improved in 85% (67 of 79) and 90% (28 of 31) of patients, respectively."	3.11	Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. ( Bairey, O; Barr, PM; Burger, JA; Coutre, SE; Dearden, C; Ghia, P; Grosicki, S; Hillmen, P; Hsu, E; Kipps, TJ; Li, JY; McCarthy, H; Moreno, C; Offner, F; Owen, C; Robak, T; Szoke, A; Tedeschi, A; Zhou, C, 2022)
" Common nonhematologic adverse events were fatigue (56%), nausea (53%), anorexia (41%), and diarrhea (41%) and were mostly low grade."	3.11	Selinexor Combined with Ibrutinib Demonstrates Tolerability and Safety in Advanced B-Cell Malignancies: A Phase I Study. ( Baker, S; Bhat, S; Byrd, JC; Canfield, D; Cempre, CB; Fu, Q; Hu, B; Huang, Y; Jaglowski, SM; Lapalombella, R; Lockman, H; Rogers, KA; Ruppert, AS; Shah, H; Stephens, DM; Vadeboncoeur, R; Walker, JS; Woyach, JA, 2022)
" Ruxolitinib dosing was based on a previous phase I trial."	3.01	Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial. ( Gallagher, J; Luo, Y; Shi, Y; Spaner, DE; Tsui, H; Wang, G, 2021)
"Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred."	3.01	Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial. ( Akber, M; Aleman, S; Bergman, P; Blennow, O; Blixt, L; Bogdanovic, G; Buggert, M; Chen, MS; Chen, P; Friman, G; Gomez, AC; Hansson, L; Hober, S; Lindgren, G; Ljunggren, HG; Ljungman, P; Loré, K; Mielke, S; Muschiol, S; Nilsson, P; Nordlander, A; Norlin, AC; Nowak, P; Österborg, A; Smith, CIE; Söderdahl, G; Thalme, A; Valentini, D; Vesterbacka, J; Wahren-Borgström, E; Wullimann, D, 2021)
" Most common adverse events (AEs) leading to prior KI discontinuation were rash (27%), arthralgia (18%), and atrial fibrillation (16%)."	3.01	Phase 2 study of the safety and efficacy of umbralisib in patients with CLL who are intolerant to BTK or PI3Kδ inhibitor therapy. ( Barr, PM; Barrientos, JC; Brander, DM; Cheson, BD; Dorsey, C; Flinn, IW; Fonseca, GA; Ghosh, N; Hamadeh, IS; Kambhampati, S; Lamanna, N; Lansigan, F; LaRatta, N; Luning Prak, ET; Mato, AR; Miskin, HP; Pagel, JM; Paskalis, D; Pu, JJ; Rai, KR; Reeves, JA; Roeker, L; Schuster, SJ; Sitlinger, A; Skarbnik, AP; Sportelli, P; Svoboda, J; Tsao, P; Weiss, MS; Weissbrot, H, 2021)
"Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons."	3.01	Adverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202. ( Abramson, JS; Bartlett, NL; Booth, AM; Brander, DM; Brown, JR; Byrd, JC; Coutre, S; Ding, W; Erba, H; Kuzma, CS; Larson, RA; Little, RF; Litzow, M; Mandrekar, SJ; Nattam, S; Owen, C; Ruppert, AS; Smith, SE; Stone, RM; Woyach, JA, 2021)
" Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time."	2.94	Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. ( Bairey, O; Barr, PM; Burger, JA; Coutre, SE; Dai, S; Dean, JP; Devereux, S; Ghia, P; Grosicki, S; Hillmen, P; Kipps, TJ; Lal, I; McCarthy, H; Moreno, C; Offner, F; Owen, C; Robak, T; Simpson, D; Tedeschi, A, 2020)
"Treatment standards for chronic lymphocytic leukemia (CLL) have been transformed with the advent of effective inhibitors of B-cell receptor signaling such as ibrutinib - a first-in-class inhibitor of BTK."	2.94	ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. ( Brown, JR; Cohen, A; Eichhorst, BF; Hilger, J; Hillmen, P; Huang, J; Lamanna, N; O'Brien, SM; Qiu, L; Salmi, T; Tam, CS; Wu, K, 2020)
"Lymphocytosis is a common and predictable pharmacodynamic effect of ibrutinib treatment, and in the absence of other signs of progression, does not represent disease progression."	2.90	Characterizing the kinetics of lymphocytosis in patients with chronic lymphocytic leukemia treated with single-agent ibrutinib. ( Barrientos, JC; Burger, JA; Byrd, JC; Hillmen, P; James, DF; Kipps, TJ; Ninomoto, J; Zhou, C, 2019)
" The recommended phase 2 dose of umbralisib when given in combination with ibrutinib was 800 mg once daily."	2.90	Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1-1b study. ( Arnason, JE; Bazemore, J; Boruchov, AM; Brown, JR; Davids, MS; Fisher, DC; Francoeur, K; Hellman, JM; Jacobsen, ED; Jacobson, CA; Kim, HT; Maegawa, R; Miskin, HP; Nicotra, A; Rueter, J; Savell, A; Sportelli, P; Stampleman, L, 2019)
" The most common all-grade adverse events were diarrhoea (47 [33%] of 141 patients), neutropenia (44 [31%]), and fatigue (37 [26%])."	2.90	Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. ( Alvarez, J; Avivi, I; Balasubramanian, S; Ben-Yehuda, D; Bosch, F; Brody, J; Buglio, D; Caballero Barrigón, MD; Carpio, C; Ceulemans, R; Cordoba, R; de Jong, J; Demirkan, F; Ferhanoglu, B; Fourneau, N; Hellmann, A; Hodkinson, BP; Horowitz, NA; Jurczak, W; Kuss, B; Lopez-Guillermo, A; Ma, DDF; Marlton, P; Nagler, A; Ozcan, M; Schaffer, M; Streit, M; Wang, SS; Wrobel, T; Yağci, M; Younes, A, 2019)
" Here, we describe the pharmacokinetic (PK) observations, along with modeling to further explore the interaction between ibrutinib and rituximab."	2.90	Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial. ( Avigdor, A; Bartlett, N; Cramer, P; de Jong, J; De Nicolao, G; Demirkan, F; Dilhuydy, MS; Fraser, G; Ganguly, S; Goy, A; Howes, A; Lavezzi, SM; Loscertales, J; Mahler, M; Neyens, M; Poggesi, I; Rule, S; Salman, M; Samoilova, O, 2019)
" In the integrated analysis (ibrutinib treatment up to 43 months), the most common adverse events (AEs) were primarily grade 1/2; diarrhea (n = 173, 52% any-grade; n = 15, 5% grade 3) and fatigue (n = 119, 36% any-grade; n = 10, 3% grade 3)."	2.90	Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. ( Barr, PM; Barrientos, JC; Burger, JA; Byrd, JC; Chang, S; Coutre, SE; Dean, JP; Devereux, S; Furman, RR; Ghia, P; Hillmen, P; James, DF; Kipps, TJ; Moreno, C; O'Brien, SM; O'Dwyer, M; Robak, T; Schuh, A; Valentino, R, 2019)
"The treatment of chronic lymphocytic leukemia (CLL) has been revolutionized by targeted therapies that either inhibit proliferation (ibrutinib) or reactivate apoptosis (venetoclax)."	2.90	Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study. ( Bishop, R; Bloor, A; Boucher, R; Brock, K; Devereux, S; Fegan, C; Forconi, F; Fox, CP; Gribben, JG; Hillmen, P; MacDonald, D; McCaig, A; Munir, T; Muñoz-Vicente, S; Patten, PEM; Pettitt, A; Rawstron, AC; Schuh, A; Yates, FJ, 2019)
"After minimal residual disease-guided treatment (day 1 of month 16), 84 (62%, 90% CI 55-69) of 135 patients (ITT population) achieved a complete response with bone marrow minimal residual disease of less than 0·01%."	2.90	Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial. ( Aanei, C; Aurran, T; Banos, A; Carassou, P; Cartron, G; Cymbalista, F; Dartigeas, C; de Guibert, S; Delmer, A; Dilhuydy, MS; Feugier, P; Fornecker, LM; Laribi, K; Le Garff-Tavernier, M; Leblond, V; Lepretre, S; Letestu, R; Lévy, V; Mahe, B; Michallet, AS; Nguyen-Khac, F; Orsini, F; Pegourie, B; Portois, C; Rouille, V; Salles, G; Subtil, F; Ticchioni, M; Tomowiak, C; Tournilhac, O; Truchan Graczyk, M; Villemagne, B; Vilque, JP; Ysebaert, L, 2019)
" Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia."	2.87	Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. ( Barr, PM; Byrd, JC; Cheson, BD; Choi, M; Chyla, B; Coutre, S; Davids, MS; Furman, RR; Humerickhouse, RA; Jones, JA; Lamanna, N; Mato, AR; Potluri, J; Salem, AH; Verdugo, M; Wierda, WG; Woyach, J; Zhou, L, 2018)
"We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators."	2.87	Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Mantle Cell Lymphoma. ( Barr, PM; Burger, JA; Chang, S; Coutre, S; Cramer, P; Dilhuydy, MS; Fraser, G; Graef, T; Hess, G; Hillmen, P; Howes, A; James, DF; Liu, E; Moreno, C; O'Brien, S; Patel, K; Styles, L; Tedeschi, A; Valentino, R; Vermeulen, J, 2018)
" To test this postulate, a pilot study (NCT02801578) was designed to systematically reduce ibrutinib dosing within the same patient with CLL over the course of three 28-day cycles."	2.87	A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. ( Bose, P; Chen, LS; Cruz, ND; Feng, S; Gandhi, V; Huang, X; Jain, N; Jiang, Y; Keating, MJ; Kroll, MH; Qiao, W; Thompson, PA; Wierda, WG; Wu, Q, 2018)
"Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance."	2.84	BTK ( Abruzzo, L; Andritsos, LA; Awan, FT; Blachly, JS; Blum, KA; Byrd, JC; Chase, W; Coleman, J; Davis, M; Doong, TJ; Flynn, JM; Gordon, A; Grever, MR; Guinn, D; Heerema, NA; Jaglowski, S; Johnson, AJ; Jones, D; Jones, JA; Lehman, A; Lozanski, A; Lozanski, G; Lucas, M; Maddocks, K; Mantel, R; McWhorter, S; Ny, F; Rogers, K; Ruppert, AS; Smith, LL; Woyach, JA; Zhao, W, 2017)
"Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially."	2.84	Ibrutinib treatment improves T cell number and function in CLL patients. ( Andritsos, LA; Awan, F; Beckwith, K; Byrd, JC; Caligiuri, MA; Cheney, C; Do, P; Flynn, JM; Fraietta, JA; Gordon, A; Johnson, AJ; Jones, JA; June, CH; Lehman, AM; Long, M; Maddocks, KJ; Maus, MV; Mundy, BL; Muthusamy, N; Woyach, JA, 2017)
"Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents."	2.84	The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy. ( Bozic, I; Burger, JA; Cibulskis, C; Farooqui, MZH; Fein, J; Getz, G; Herman, SEM; Hoellenriegel, J; Landau, DA; Leshchiner, I; Liu, D; Livitz, D; Neuberg, DS; Ravichandran, S; Rosebrock, D; Sivina, M; Sun, C; Underbayev, C; Wiestner, A; Wu, CJ; Zhang, W; Zviran, A, 2017)
" Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event."	2.84	Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial. ( Brooks, HD; Burke, JM; Fanning, S; Farber, CM; Greenwald, DR; Klein, L; Kolibaba, KS; Mahadevan, D; Miskin, HP; Schreeder, MT; Sharman, JP; Sportelli, P; Weiss, MS, 2017)
"The increasing indications and addition of newer agents to clinical practice and emergence of BTK inhibitor-related cardiac adverse events have complicated the management decisions for utilization of this class of therapy."	2.82	Cardiotoxicity of BTK inhibitors: ibrutinib and beyond. ( Awan, FT; Christensen, BW; Zaha, VG, 2022)
" We also synopsize and discuss the cardiovascular adverse effects related to other more selective BTK inhibitors, which may guide the selection of appropriate BTK inhibitors."	2.82	Ibrutinib-Associated Cardiotoxicity: From the Pharmaceutical to the Clinical. ( Dong, R; Lin, N; Tan, B; Yan, Y; Zeng, X, 2022)
"Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group)."	2.82	Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. ( Avigdor, A; Balasubramanian, S; Bartlett, NL; Chanan-Khan, A; Cramer, P; Demirkan, F; Dilhuydy, MS; Fraser, G; Goy, A; Grosicki, S; Hallek, M; Howes, A; Janssens, A; Karlsson, C; Loscertales, J; Mahler, M; Mato, A; Mayer, J; Panagiotidis, P; Pavlovsky, MA; Phelps, C; Pristupa, A; Pylypenko, H; Rule, S; Salman, M; Samoilova, O; Silva, RS; Sun, S; Villa, D, 2016)
"A T-cell defect in chronic lymphocytic leukemia (CLL) due to disease and/or therapy impairs ex vivo expansion and response to CAR T cells."	2.82	Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. ( Barrett, DM; Beckwith, KA; Byrd, JC; Cogdill, AP; Cook, DR; Do, P; Fraietta, JA; Gill, S; Hulitt, J; Johnson, AJ; June, CH; Kudchodkar, SB; Lacey, SF; Levine, BL; Long, M; Maddocks, K; Maus, MV; McGettigan, SE; Melenhorst, JJ; Muthusamy, N; Patel, PR; Porter, DL; Ruella, M; Woyach, JA; Xu, J; Zhang, C; Zheng, Z, 2016)
" We developed a population pharmacokinetic (PK) model for ibrutinib in patients."	2.80	Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. ( Advani, R; Byrd, JC; de Jong, J; De Nicolao, G; de Trixhe, XW; Loury, D; Marostica, E; McGreivy, J; O'Brien, S; Poggesi, I; Sukbuntherng, J; Vermeulen, A, 2015)
" When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable."	2.80	The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia. ( Byrd, JC; Chauhan, V; de Jong, J; Hellemans, P; James, D; Jiao, J; Loury, DJ; Mannaert, E; Murphy, J; O'Brien, S; Skee, D; Sukbuntherng, J, 2015)
"Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity."	2.80	The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. ( Barr, PM; Barrientos, JC; Brown, JR; Burger, JA; Clow, F; Flinn, IW; Friedberg, JW; Graef, T; James, DF; O'Brien, S; Rai, K; Tran, A, 2015)
" The most frequent adverse events (any grade) were diarrhea (70%), infusion-related reaction (45%), and peripheral sensory neuropathy (44%)."	2.80	Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. ( Andritsos, LA; Blum, KA; Byrd, JC; Flynn, JM; Grever, MR; Hall, N; Heerema, NA; Jaglowski, SM; James, DF; Johnson, AJ; Jones, JA; Lozanski, G; Maddocks, KJ; Munneke, B; Nagar, V; Neuenburg, JK; Ruppert, AS; Smucker, K; Stefanos, M; West, JS; Woyach, JA, 2015)
"Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events."	2.80	Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib. ( Cullinane, AM; Farooqui, MZ; Herman, SE; Holland, SM; Lipsky, AH; Lozier, JN; Marti, G; Martyr, S; Nghiem, K; Niemann, CU; Saba, N; Soto, S; Sun, C; Tian, X; Uzel, G; Valdez, J; Wiestner, A, 2015)
"The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid."	2.79	Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. ( Aue, G; Calvo, KR; Farooqui, M; Geisler, CH; Gyamfi, JA; Herman, SE; Jones, J; Lipsky, A; Liu, D; Maric, I; Marti, GE; Martyr, S; Mustafa, RZ; Niemann, CU; Pedersen, LB; Saba, N; Soto, S; Valdez, J; Wiestner, A, 2014)
"The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions."	2.78	Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. ( Blum, KA; Buggy, JJ; Burger, JA; Byrd, JC; Chang, BY; Clow, F; Coleman, M; Coutre, SE; Flinn, IW; Furman, RR; Grant, B; Hedrick, E; Heerema, NA; James, DF; Johnson, AJ; Jones, JA; O'Brien, S; Sharman, JP; Sukbuntherng, J; Wierda, WG; Zhao, W, 2013)
" The pharmacokinetic and pharmacodynamic data of acalabrutinib were also discussed."	2.72	Assessing the pharmacokinetics of acalabrutinib in the treatment of chronic lymphocytic leukemia. ( Li, J; Miao, Y; Xu, W, 2021)
"Whether this affects infection susceptibility and vaccination efficacy requires further investigation."	2.72	BTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects. ( Mulder, TA; Österborg, A; Palma, M, 2021)
"The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world."	2.72	Keeping a balance in chronic lymphocytic leukemia (CLL) patients taking ibrutinib: ibrutinib-associated adverse events and their management based on drug interactions. ( Baek, DW; Cho, HJ; Kim, J; Lee, JM; Moon, JH; Sohn, SK, 2021)
" In vitro exposure of leukemia cells to CAde showed that it was eight times less toxic as compared to CdA."	2.71	Cytotoxicity and pharmacokinetics of cladribine metabolite, 2-chloroadenine in patients with leukemia. ( Albertioni, F; Juliusson, G; Larsson, R; Liliemark, J; Lindemalm, S, 2004)
"A major revolution in the treatment of chronic lymphocytic leukemia (CLL) began with the approval of ibrutinib, a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK), for the treatment of relapsed/refractory (R/R) and/or TP53 mutated patients with CLL."	2.66	Ibrutinib in the treatment of chronic lymphocytic leukemia: 5 years on. ( Matutes, E; Molica, S; Polliack, A; Tam, C, 2020)
"Advances in the molecular biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and development of molecularly targeted therapies have resulted in treatment innovations."	2.66	Evolution in the management of chronic lymphocytic leukemia in Japan: should MRD negativity be the goal? ( Suzumiya, J; Takizawa, J, 2020)
"Chronic lymphocytic leukemia is one of the most common lymphoid malignancies."	2.66	Updates in the management of chronic lymphocytic leukemia/small lymphocytic leukemia. ( Hanna, KS, 2020)
"Here, we report a case of an elderly chronic lymphocytic leukemia patient who developed multiple inflamed lesions and lower limb cellulitis in 100 days after initiating ibrutinib therapy."	2.66	Ibrutinib-associated sever skin toxicity: A case of multiple inflamed skin lesions and cellulitis in a 68-year-old male patient with relapsed chronic lymphocytic leukemia - Case report and literature review. ( Albattah, A; Alhijji, I; Alokka, R; Elazzazy, S; Ghasoub, R; Nemir, A; Taha, R, 2020)
"Chronic lymphocytic leukemia has a highly variable disease course across patients, thought to be driven by the vast inter- and intrapatient molecular heterogeneity described in several large-scale DNA-sequencing studies conducted over the past decade."	2.61	Clonal dynamics in chronic lymphocytic leukemia. ( Gutierrez, C; Wu, CJ, 2019)
"The management of chronic lymphocytic leukemia (CLL) has undergone dramatic changes over the previous 2 decades with the introduction of multiple new therapies and new combinations."	2.61	Treatment-naive CLL: lessons from phase 2 and phase 3 clinical trials. ( Woyach, JA, 2019)
" Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas."	2.61	Case series of unique adverse events related to the use of ibrutinib in patients with B-cell malignancies-A single institution experience and a review of literature. ( Albrethsen, M; Chilkulwar, A; Faisal, MS; Fazal, S; Khattab, A; Sadashiv, S; Shaikh, H, 2019)
"Moving from the recognition that infection control represents an unmet need, the Italian Society of Hematology (SIE) convened a panel of experts who had published and/or expressed an interest in infection complications in CLL."	2.61	Infection control in patients treated for chronic lymphocytic leukemia with ibrutinib or idelalisib: recommendations from Italian society of hematology. ( Barosi, G; Gaidano, G; Girmenia, C; Marchetti, M; Pane, F; Rambaldi, A; Tura, S; Zinzani, PL, 2019)
"Waldenström's macroglobulinemia (WM) is a rare, incurable hematologic disorder with a relatively indolent course in a majority of the patients."	2.61	Updates in prognostication and treatment of Waldenström's macroglobulinemia. ( Advani, P; Ailawadhi, S; Paulus, A, 2019)
"Discussion One patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and one patient with mantle cell lymphoma developed laboratory and clinical tumor lysis syndrome following initiation of ibrutinib therapy."	2.58	Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature. ( Brown, JN; Hammond, JM; Titus-Rains, KS, 2018)
"Those who develop disease progression on ibrutinib are a particularly high-risk population with poor outcomes."	2.58	Management of patients with chronic lymphocytic leukemia at high risk of relapse on ibrutinib therapy. ( Ayed, AO; Parikh, SA, 2018)
"While opportunistic infections and viral reactivations occur with both ibrutinib and idelalisib, these complications are less common and less severe with ibrutinib, especially when used as monotherapy without additional immunosuppressive agents."	2.58	Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia. ( Pleyer, C; Sun, C; Wiestner, A, 2018)
"The treatment landscape of chronic lymphocytic leukemia (CLL) has changed dramatically in the last few years."	2.58	Selecting Frontline Therapy for CLL in 2018. ( Jain, N, 2018)
"Although the therapy of chronic lymphocytic leukemia (CLL) has changed rapidly over the last 5 years, the key considerations in selecting a therapy for a previously treated patient with CLL continue to include the nature of the prior therapy and the duration of prior remission to that therapy, the prognostic features of the disease, and the health and comorbidities of the patient in question."	2.58	Relapsed CLL: sequencing, combinations, and novel agents. ( Brown, JR, 2018)
" With remarkable efficacy, good oral bioavailability, and modest adverse events profile, ibrutinib use is likely to continue to increase."	2.55	Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib. ( Kaur, V; Swami, A, 2017)
" Here, we review the available literature on the pharmacokinetic and pharmacodynamic properties of these novel agents to guide the reader in the appropriate use of ibrutinib, idelalisib, and venetoclax."	2.55	Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Chronic Lymphocytic Leukemia: Ibrutinib, Idelalisib, and Venetoclax. ( Hill, BT; Waldron, M; Winter, A, 2017)
"The therapy for chronic lymphocytic leukemia (CLL) is undergoing a major transformation."	2.55	Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future. ( Molica, S, 2017)
"Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy."	2.55	Advances in the treatment of relapsed/refractory chronic lymphocytic leukemia. ( Bence-Bruckler, I; Coutre, S; Delage, R; Owen, CJ; Shustik, C; Toze, CL, 2017)
"Patients with chronic lymphocytic leukemia (CLL) having a chromosomal loss on the short arm of chromosome 17 including the TP53 gene locus (17p deletion) and/or having mutations in TP53 have a short overall survival and, until recently, limited treatment options."	2.55	Managing Patients With TP53-Deficient Chronic Lymphocytic Leukemia. ( Edelmann, J; Gribben, JG, 2017)
"Treatment options for chronic lymphocytic leukemia, the most common leukemia in the United States, have expanded rapidly in recent years."	2.55	Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. ( Marini, BL; Perissinotti, AJ; Samanas, L, 2017)
" In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs."	2.53	A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib. ( Kim, SS; Lee, CS; Rattu, MA, 2016)
"The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise."	2.52	BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future. ( de Rooij, MF; Eldering, E; Kater, AP; Spaargaren, M, 2015)
"Idelalisib has shown efficacy in the relapsed setting and is currently approved by the FDA for use in combination with rituximab."	2.52	Three newly approved drugs for chronic lymphocytic leukemia: incorporating ibrutinib, idelalisib, and obinutuzumab into clinical practice. ( Burger, JA; Keating, MJ; O'Brien, SM; Sanford, DS; Wierda, WG, 2015)
" Ibrutinib is an orally bioavailable and highly specific BTK inhibitor that was recently approved for treatment of patients with recurrent CLL and mantle cell lymphoma (MCL)."	2.52	Mechanisms of ibrutinib resistance in chronic lymphocytic leukaemia and non-Hodgkin lymphoma. ( Lynn Wang, Y; Smith, SM; Zhang, SQ; Zhang, SY, 2015)
" Discontinuation of ibrutinib is rarely due to adverse events related to the drug."	2.52	The clinical safety of ibrutinib in chronic lymphocytic leukemia. ( Molica, S, 2015)
" Orally bioavailable inhibitors of spleen tyrosine kinase, Bruton's tyrosine kinase, or PI3Kδ, induce high rates of durable responses."	2.52	The role of B-cell receptor inhibitors in the treatment of patients with chronic lymphocytic leukemia. ( Wiestner, A, 2015)
"The leukemic B cells from patients with chronic lymphocytic leukemia (CLL) require interactions with non-malignant cells and matrix in the tissue microenvironment to survive and grow."	1.91	Functional consequences of inhibition of Bruton's tyrosine kinase by ibrutinib in chronic lymphocytic leukemia. ( Chen, SS; Chiorazzi, N, 2023)
"The "accelerated" chronic lymphocytic leukemia (aCLL) is a relatively rare form of CLL progression."	1.72	Atypical "accelerated" chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica. ( Yavorkovsky, LL, 2022)
"A 79-year-old female was diagnosed with chronic lymphocytic leukemia seven years prior."	1.72	[Disseminated cryptococcosis during ibrutinib treatment for chronic lymphocytic leukemia]. ( Kumekawa, H; Mizuchi, D; Tamura, K; Watanabe, D, 2022)
"Blood was obtained from patients with chronic lymphocytic leukemia, mantle-cell lymphoma and Waldenström macroglobulinemia with and without ibrutinib treatment and perfused through a microfluidic channel with(out) 60% stenosis over Horm type I collagen or human atherosclerotic plaque homogenate."	1.72	The effect of Bruton's tyrosine kinase inhibitor ibrutinib on atherothrombus formation under stenotic flow conditions. ( Claushuis, TAM; Cosemans, JMEM; D'Italia, G; Karel, MFA; Kuijpers, MJE; Lemmens, TP; Tullemans, BME, 2022)
"Primary myelofibrosis (PMF) is not commonly associated with CLL, with only a few cases reported in the literature, with little information regarding the clinico-biological features and the optimal management for these associated conditions."	1.72	Primary Myelofibrosis Occurring during Targeted Therapy for Chronic Lymphocytic Leukemia: A Report of Two Cases. ( Angotzi, F; Bertorelle, R; Binotto, G; Cellini, A; Dei Tos, AP; Pizzi, M; Scarmozzino, F; Trentin, L; Visentin, A, 2022)
"Patients with chronic lymphocytic leukemia (CLL) relapsing on ibrutinib are often treated with the Bcl-2 inhibitor venetoclax."	1.72	Two Distinct Clinical Patterns of Ibrutinib-to-Venetoclax Transition in Relapsed Chronic Lymphocytic Leukemia Patients. ( Ferrarini, I; Gandini, F; Rigo, A; Zapparoli, E, 2022)
"Certain genetic features in chronic lymphocytic leukemia (CLL) are associated with inferior outcomes after chemoimmunotherapy (CIT)."	1.72	Real-world Clinical Outcomes of First-Line Ibrutinib or Chemoimmunotherapy in Patients with Chronic Lymphocytic Leukemia by Risk Status. ( Deering, KL; Harshaw, Q; Huang, Q; Leslie, LA, 2022)
" Adverse events occurred in 74."	1.72	Efficacy and safety of ibrutinib in relapsed/refractory CLL and SLL in Japan: a post-marketing surveillance. ( Akizuki, R; Fujino, A; Nomura, F; Omi, A; Tsujioka, S, 2022)
" Toxic effects of the combination of ibrutinib and cetuximab have been reported in a patient with metastatic CRC."	1.72	Ibrutinib and panitumumab used in combination safely in a patient with metachronous colorectal cancer and chronic lymphocytic leukemia. ( Araz, M; Artaç, M; Çeneli, Ö; Karaağaç, M; Karakurt Eryilmaz, M; Korkmaz, M, 2022)
"BACKGROUND Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm and the most common leukemia in adults in Western countries."	1.72	An 81-Year-Old Man with a 6-Year History of Chronic Lymphocytic Leukemia Presenting with Disease Flare Following Ibrutinib Discontinuation. ( Colaci, E; Giusti, D; Leonardi, G; Luppi, M; Maccaferri, M; Marasca, R; Pioli, V; Potenza, L; Pozzi, S, 2022)
"Among patients with CLL disease progression on ibrutinib, OS was significantly longer when next-line treatment was chimeric antigen receptor T-cell therapy (median not reached) or venetoclax-based treatment (median 29."	1.72	Clinical outcomes in patients with chronic lymphocytic leukemia with disease progression on ibrutinib. ( Ailawadhi, S; Braggio, E; Call, TG; Chanan-Khan, AA; Ding, W; Hampel, PJ; Hanson, CA; Kay, NE; Kenderian, SS; Koehler, AB; Leis, JF; Muchtar, E; Parikh, SA; Parrondo, R; Rabe, KG; Schwager, SM; Sher, T; Shi, M; Slager, SL; Van Dyke, DL; Wang, Y, 2022)
"Chylothorax is an infrequent pleural effusion often caused by traumatic or nontraumatic injury to the thoracic duct."	1.72	Complete resolution of chylothorax with ibrutinib in chronic lymphocytic leukemia: a case report. ( Cheng, L; Huang, M; Jiang, L; Wei, J; Xu, H; Zhou, M, 2022)
"Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL)."	1.62	Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study. ( Abdel-Qadir, H; Austin, PC; Calvillo-Argüelles, O; Lee, DS; Leong, D; Nanthakumar, K; Pang, A; Prica, A; Sabrie, N; Thavendiranathan, P, 2021)
"In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes."	1.62	Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib? ( Baratè, C; Biagi, A; Borella, C; Cairoli, R; Cassin, R; Cavalloni, C; Chiarenza, A; Ciolli, S; Coscia, M; Del Poeta, G; Deodato, M; Di Raimondo, F; Fresa, A; Frustaci, AM; Greco, A; Ielo, C; Lapietra, G; Laurenti, L; Mauro, FR; Montillo, M; Morelli, F; Murru, R; Pelle, AC; Postorino, M; Reda, G; Rossi, V; Sportoletti, P; Tedeschi, A; Varettoni, M; Vitale, C; Zamprogna, G, 2021)
" Patient characteristics, ibrutinib use and adverse drug reactions (ADRs) were collected from medical records."	1.62	Patterns of use and safety of ibrutinib in real-life practice. ( Allouchery, M; Delaunay, P; Delwail, V; Guidez, S; Lafay-Chebassier, C; Pérault-Pochat, MC; Salvo, F; Tomowiak, C, 2021)
"ALK-positive histiocytosis is a recently described entity with few reported cases in literature."	1.62	ALK-positive histiocytosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a multitarget response under ibrutinib. ( Brousset, P; Evrard, SM; Kanoun, S; Laurent, C; Meggetto, F; Péricart, S; Syrykh, C; Ysebaert, L, 2021)
" Ibrutinib is currently not available in a liquid oral dosage form."	1.62	Ibrutinib treatment via alternative administration in a patient with chronic lymphocytic leukemia and dysphagia. ( Arnall, JR; DiSogra, KY; Janes, A; Moore, DC; Park, SI; Tran, T, 2021)
"Opportunistic infections in chronic lymphocytic leukemia (CLL) have been described in clinical trials, single-center studies, and case reports."	1.62	A nationwide study on inpatient opportunistic infections in patients with chronic lymphocytic leukemia in the pre-ibrutinib era. ( Aspelund, T; Björkholm, M; Gíslason, GK; Gottfreðsson, M; Kristinsson, SY; Landgren, O; Rögnvaldsson, S; Steingrímsson, V; Turesson, I; Þorsteinsdóttir, S, 2021)
"Recirculation of chronic lymphocytic leukemia (CLL) cells between the peripheral blood and lymphoid niches plays a critical role in disease pathophysiology, and inhibiting this process is one of the major mechanisms of action for B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib."	1.62	FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia. ( Amruz Cerna, K; Benes, V; Borsky, M; Brychtova, Y; Doubek, M; Kostalova, L; Kren, L; Krivanek, J; Kudlickova Peskova, M; Liskova, K; Loja, T; Mayer, J; Mladonicka Pavlasova, G; Mraz, M; Musilova Litzmanova, K; Ondrisova, L; Oppelt, J; Panovska, A; Pospisilova, S; Seda, V; Sharma, S; Tan, Z; Verner, J; Vojackova, E; Zhang, S; Zicha, D, 2021)
" He was placed on intravenous immunoglobulin (IVIg) in combination with ibrutinib."	1.62	[Intravenous immunoglobulin in combination with ibrutinib for the treatment of IgM-type M protein associated peripheral neuropathy complicated with chronic lymphocytic leukemia]. ( Kawano, K; Kawano, Y; Miyazaki, Y; Ohtsuka, E; Saburi, M; Sakata, M; Takata, H; Uchida, H, 2021)
"A 77-year-old man with underlying chronic lymphocytic leukemia (CLL) on ibrutinib treatment was admitted because of a superinfected mosquito bite on the left ear and multiple partially necrotic skin lesions disseminated all over the entire body five days after returning from a trip to Colombia."	1.62	An Eschar-like souvenir from a journey to Colombia: Ecthyma gangrenosum as a differential diagnosis of tropical diseases in immunocompromised patients - a case report. ( Einwächter, H; Konukiewitz, B; Rothe, K; Schmid, RM; Schneider, J; Spinner, CD; Verbeek, M; Wiedemann, GM, 2021)
" While 176 adverse events (AEs) were reported in 74 (54."	1.62	Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data ( Akay, OM; Akdeniz, A; Akpınar, S; Aydoğdu, İ; Baştürk, A; Batur, DS; Berber, İ; Çekdemir, D; Çetin, G; Davulcu, EA; Demircioğlu, S; Deveci, B; Dinçyürek, HD; Doğu, MH; Durusoy, SS; Ertop, Ş; Ferhanoğlu, B; Güneş, AK; Gürkan, E; İlhan, G; Kaya, E; Kızıklı, A; Kurtoğlu, E; Mehtap, Ö; Okan, V; Okay, M; Özcan, MA; Özcan, Ö; Özet, G; Özkocamaz, V; Pepedil Tanrıkulu, F; Sahip, B; Saydam, G; Sayınalp, N; Seyhanlı, A; Sönmez, M; Terzi, H; Tombak, A; Turgut, B; Uçar, MA; Ümit, EG; Ünal, A; Yavaşoğlu, İ; Yıldırım, R; Yılmaz, M, 2021)
"NOTCH1 mutations in chronic lymphocytic leukemia (CLL) lead to accumulation of NOTCH1 intracellular domain (NICD) and prolong signaling."	1.56	Bidirectional linkage between the B-cell receptor and NOTCH1 in chronic lymphocytic leukemia and in Richter's syndrome: therapeutic implications. ( Allan, JN; Arruga, F; Bracciamà, V; Coscia, M; D'Arena, G; Deaglio, S; Forconi, F; Furman, RR; Gaidano, G; Gizzi, K; Packham, G; Vaisitti, T; Vitale, N; Yeomans, A, 2020)
"The case is here reported of a chronic lymphocytic leukemia patient with ibrutinib-induced polyneuropathy."	1.56	Ibrutinib-induced polyneuropathy: A case report. ( Albayrak, M; Cömert, P; Öztürk, HB; Reis Aras, M; Şahin, O; Yıldız, A, 2020)
"Tumor lysis syndrome is an oncologic emergency resulting from rapid and massive tumor cell death that may lead to serious clinical complications including acute kidney injury and cardiac arrest."	1.56	Bruton's tyrosine kinase inhibitors and the kidney: Focus on ibrutinib. ( Brener, H; Brener, ZZ; Losev, A, 2020)
"Ibrutinib use in chronic lymphocytic leukemia (CLL) has previously been associated with CNS-A."	1.56	Isolated central nervous system Aspergillosis infection in a chronic lymphocytic leukemia patient on Ibrutinib: A case report. ( Barnes, M; Buttar, B; Gondal, K; Kaell, A; Kumar, V; Le, TH; Siddique, H, 2020)
" The aim of this work is to develop a population pharmacokinetic model for ibrutinib and its dihydrodiol metabolite to quantify pharmacokinetic inter- and intra-individual variability, to evaluate the impact of several covariates on ibrutinib pharmacokinetic parameters, and to examine the relationship between exposure and clinical outcome."	1.56	Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies. ( Allal, B; Chatelut, E; De Barros, S; Despas, F; Dupré, L; Gallais, F; Obéric, L; Protin, C; Quillet-Mary, A; Thomas, F; White-Koning, M; Ysebaert, L, 2020)
" The purpose of this study was to describe treatment patterns, adverse events (AEs), and economic burden among treated patients with CLL."	1.56	Real-World Treatment Patterns, Adverse Events, Resource Use, and Costs Among Commercially Insured, Younger Patients with Chronic Lymphocytic Leukemia in the USA: A Retrospective Cohort Study. ( Burudpakdee, C; Kabadi, SM; Near, A; Wada, K, 2020)
"Lysosomes in chronic lymphocytic leukemia (CLL) cells have previously been identified as a promising target for therapeutic intervention in combination with targeted therapies."	1.56	Antihistamines are synergistic with Bruton's tyrosine kinase inhibiter ibrutinib mediated by lysosome disruption in chronic lymphocytic leukemia (CLL) cells. ( Chanas-Larue, A; Gibson, SB; Henson, ES; Johnston, JB; Villalpando-Rodriguez, GE, 2020)
"Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor."	1.56	Ibrutinib, a Bruton's tyrosine kinase inhibitor, a new risk factor for cryptococcosis. ( Boutoille, D; Brochard, J; Guimard, T; Le Pape, P; Leterrier, M; Mahe, B; Mahe, J; Morio, F; Morrier, M; Raffi, F, 2020)
"Novel agents have made the management of chronic lymphocytic leukemia (CLL) more promising and personalized."	1.56	Chidamide, a histone deacetylase inhibitor, inhibits autophagy and exhibits therapeutic implication in chronic lymphocytic leukemia. ( Fan, L; Kong, YL; Li, JY; Liang, JH; Pan, BH; Wang, L; Wu, JZ; Xia, Y; Xu, W; Zhu, HY, 2020)
"Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia, accounting for ≈ 37% of all leukemias in the United States."	1.56	Time to Next Treatment, Health Care Resource Utilization, and Costs Associated with Ibrutinib Use Among U.S. Veterans with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Real-World Retrospective Analysis. ( Borra, S; Huang, Q; Janjan, N; Li, J; Shrestha, S; Sundaram, M; Wang, L, 2020)
"Approximately 25% of patients with chronic lymphocytic leukemia (CLL) experience a flare of disease following ibrutinib discontinuation."	1.56	Disease Flare During Temporary Interruption of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia. ( Braggio, E; Call, TG; Ding, W; Fonder, AL; Hampel, PJ; Kay, NE; Kenderian, SS; Koehler, AB; Leis, JF; Muchtar, E; Parikh, SA; Rabe, KG; Schwager, SM; Slager, SL; Van Dyke, DL; Wang, Y; Witzig, TE, 2020)
"The clinical course of chronic lymphocytic leukemia (CLL) is often complicated by autoimmune cytopenia (AIC)."	1.51	[Improvement of autoimmune cytopenia with ibrutinib in a chronic lymphocytic leukemia patient complicated by monoclonal immunoglobulin deposition disease]. ( Hara, S; Ishikawa, T; Nakamura, M; Yamashita, D; Yoshioka, S, 2019)
" Submaximal ibrutinib dosing will have to be further systematically evaluated."	1.51	Descriptive analysis of dosing and outcomes for patients with ibrutinib-treated relapsed or refractory chronic lymphocytic leukemia in a Canadian centre. ( Banerji, V; Brown, K; Bucher, O; Dawe, DE; Dhaliwal, DH; Geirnaert, M; Hibbert, I; Johnston, JB; Uminski, K, 2019)
"After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases."	1.51	Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia. ( Bachy, E; Baseggio, L; Besson, H; Callet-Bauchu, E; Diels, J; Doubek, M; Garside, J; Healy, N; Hermans, R; Iraqi, W; Lundbom, J; Lysak, D; Panovska, A; Pick-Lauer, C; Salles, G; Simkovic, M; Smolej, L; Spacek, M; Urbanova, R, 2019)
"The median times to disease progression and RT were 33."	1.51	Targeted multigene deep sequencing of Bruton tyrosine kinase inhibitor-resistant chronic lymphocytic leukemia with disease progression and Richter transformation. ( Alhalouli, T; Bueso-Ramos, C; Burger, J; Estrov, Z; Ferrajoli, A; Jain, N; Jain, P; Kanagal-Shamanna, R; Kantarjian, HM; Keating, M; Khoury, JD; Luthra, R; Medeiros, LJ; Patel, KP; Routbort, M; Wierda, W, 2019)
"These CLL-like cells show genome instability and dysregulation of multiple CLL-associated cellular processes, including deregulated B cell receptor signaling, which we also identified in human CLL cases."	1.51	A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion. ( Brooks, AN; Campagna, DR; Carrasco, RD; Cartun, ZJ; Cibulskis, CL; DeCaprio, JA; Ebert, BL; Fan, J; Fleming, MD; Gambe, RG; Getz, G; Ghia, EM; Herman, SEM; Kipps, TJ; Leshchiner, I; Martinez, AZ; Neuberg, D; Obeng, EA; Rassenti, LZ; Reed, R; Regis, FFD; Sun, J; Taylor-Weiner, A; Ten Hacken, E; Wan, Y; Wang, L; Wiestner, A; Wu, CJ; Yin, S, 2019)
" Emerging real-world-data shows similar response and survival, but higher discontinuation rates due to adverse events (AEs)."	1.51	Safety and efficacy analysis of long-term follow up real-world data with ibrutinib monotherapy in 58 patients with CLL treated in a single-center in Greece. ( Angelopoulou, M; Bitsani, C; Dimou, M; Iliakis, T; Kalyva, S; Koudouna, A; Kyrtsonis, MC; Panayiotidis, P; Papaioannou, P; Pardalis, V; Tsaftaridis, P; Vassilakopoulos, TP, 2019)
"In primary chronic lymphocytic leukemia (CLL) lymphocytes, pharmacological interference with mitochondrial ATP synthesis or glucose metabolism affects BTK activity."	1.51	Bruton's tyrosine kinase is at the crossroads of metabolic adaptation in primary malignant human lymphocytes. ( Aloyz, R; Doyon, D; Paliouras, M; Sharif-Askari, B, 2019)
"Neutrophilic panniculitis is a relatively rare condition, characterized by predominantly neutrophilic inflammation in the subcutaneous fat."	1.48	Self-limiting Ibrutinib-Induced Neutrophilic Panniculitis. ( Bayers, S; Stewart, J; Vandergriff, T, 2018)
" To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation and impact on cell migration."	1.48	Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy. ( Ayres, ML; Balakrishnan, K; Cheung, JP; Gandhi, V; Gay, J; Ivan, C; Keating, MJ; Lamothe, B; Marszalek, JR; Morse, J; Nelson, M; Patel, VK; Wierda, WG, 2018)
"Ibrutinib represents a revolution in chronic lymphocytic leukemia treatment scenario providing results never seen before and offering an effective therapy even in high-risk patients with really poor outcome after chemoimmunotherapy."	1.48	Ibrutinib and its use in the treatment of chronic lymphocytic leukemia. ( Cairoli, R; Deodato, M; Frustaci, AM; Mazzucchelli, M; Montillo, M; Tedeschi, A, 2018)
"Results from several recent studies in chronic lymphocytic leukemia (CLL) have demonstrated an association between ibrutinib exposure and the development of atrial fibrillation, estimated incidence of 11% with long-term follow up."	1.48	Left atrial abnormality (LAA) as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia. ( Ali, N; Carver, J; Clasen, S; Gashonia, L; Hughes, M; Mato, AR; Nabhan, C; Pickens, P; Rhodes, J; Schuster, S; Svoboda, J, 2018)
"We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either commercially or on clinical trials."	1.48	Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. ( Bachow, SH; Barr, P; Brander, DM; Cheson, BD; Claxton, D; Dorsey, C; Goy, A; Hill, B; Howlett, C; Isaac, K; Kennard, KH; Kiselev, P; Lamanna, N; Landsburg, D; Mato, AR; Nabhan, C; Nasta, SD; Pu, J; Schuster, SJ; Skarbnik, A; Svoboda, J; Thompson, MC; Timlin, C; Ujjani, CS; Winter, A; Zent, C, 2018)
"Invasive bacterial infections developed in 23 (53."	1.48	Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer. ( Cohen, N; Hohl, TM; Palomba, ML; Redelman-Sidi, G; Seo, SK; Taur, Y; Varughese, T, 2018)
"Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities."	1.48	Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib. ( Alqahtani, H; Amrock, SM; Choi, M; Churnetski, M; Cohen, JB; Danilov, AV; Gordon, MJ; Hoff, S; James, S; Kittai, A; Manda, S; Persky, D; Rivera, X; Spurgeon, SE, 2018)
"There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib."	1.48	Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia. ( Gabcova, G; Gajdos, P; Kriegova, E; Manukyan, G; Mikulkova, Z; Papajik, T; Smotkova Kraiczova, V; Turcsanyi, P; Urbanova, R; Zehnalova, S, 2018)
" These findings suggest deterioration of the humoral immune system is associated with progressive CLL and altering the dosing of IgRT to achieve higher than conventional IgG target levels may have therapeutic activity."	1.48	Association of blood IgG with tumor necrosis factor-alpha and clinical course of chronic lymphocytic leukemia. ( Huang, J; Lazarus, A; Norris, P; Shi, Y; Spaner, DE; Venema, R; Wang, G, 2018)
"Although the treatment paradigm for chronic lymphocytic leukemia (CLL) is rapidly changing, the disease remains incurable, except with allogeneic bone marrow transplantation, and resistance, relapsed disease, and partial responses persist as significant challenges."	1.48	Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia. ( Achille, A; Deng, S; Fonseca, R; Jones, SS; Maharaj, K; Pabon-Saldana, M; Pinilla-Ibarz, J; Powers, JJ; Quayle, SN; Sahakian, E; Sotomayor, EM; Villagra, A, 2018)
"The established treatment algorithms for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are currently challenged by novel classes of drugs, with ibrutinib being one of the most effective."	1.46	Hodgkin Lymphoma Transformation of Chronic Lymphocytic Leukemia Under Ibrutinib Therapy: Chance Association or Therapy-related? ( Kalpadakis, C; Koulieris, E; Moschogiannis, M; Pangalis, GA; Rontogianni, D; Sachanas, S; Tsirkinidis, P; Yiakoumis, X, 2017)
"Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0."	1.46	Emergence of Bruton's tyrosine kinase-negative Hodgkin lymphoma during ibrutinib treatment of chronic lymphocytic leukaemia. ( Catherwood, M; Glavey, S; Leader, M; Marafioti, T; McCartney, Y; McCloy, M; Murphy, P; Quinn, J; Sargent, J; Thornton, P, 2017)
"Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range."	1.46	The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells through the upregulation of NOXA and synergizes with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax. ( Albericio, F; Cosialls, AM; de la Banda, E; Gil, J; González-Barca, EM; González-Gironès, DM; Iglesias-Serret, D; Lavilla, R; Núñez-Vázquez, S; Pomares, H; Pons, G; Preciado, S; Saura-Esteller, J, 2017)
"Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments."	1.46	Ibrutinib treatment of a patient with relapsing chronic lymphocytic leukemia and sustained remission of Richter syndrome. ( Albi, E; Ascani, S; Aureli, P; Baldoni, S; Del Papa, B; Di Ianni, M; Dorillo, E; Falzetti, F; Sportoletti, P, 2017)
"Here we show that treatment of chronic lymphocytic leukemia cells (CLL) with IT-901 effectively interrupts NF-κB transcriptional activity."	1.46	Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor. ( Allan, JN; Arruga, F; Deaglio, S; Furman, RR; Gaudino, F; Liou, HC; Moscvin, M; Ouk, S; Serra, S; Vaisitti, T; Vitale, N; Zakrzewski, JL, 2017)
"The lymph node (LN) is the site of chronic lymphocytic leukemia (CLL) cell activation and proliferation."	1.46	Ibrutinib downregulates a subset of miRNA leading to upregulation of tumor suppressors and inhibition of cell proliferation in chronic lymphocytic leukemia. ( Abdelghaffar, HA; Abousamra, NK; Anastas, V; Barber, E; Calvo, KR; Corrigan-Cummins, M; Elbaz, O; Farooqui, M; Herman, SE; Saba, NS; Saleh, LM; Sarasua, SM; Sun, C; Wang, W; Wiestner, A; Zhao, Z, 2017)
"Patients with chronic lymphocytic leukemia (CLL) that develop resistance to Bruton tyrosine kinase (BTK) inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2)."	1.46	Using high-sensitivity sequencing for the detection of mutations in BTK and PLCγ2 genes in cellular and cell-free DNA and correlation with progression in patients treated with BTK inhibitors. ( Ahn, I; Albitar, A; Albitar, M; DeDios, I; Estella, J; Farooqui, M; Ma, W; Wiestner, A, 2017)
"A group of experts from the Spanish Chronic Lymphocytic Leukemia Group reviewed all published literature from January 2010 to January 2016, in order to provide recommendations based on clinical evidence."	1.46	Update of the Grupo Español de Leucemia Linfocítica Crónica clinical guidelines of the management of chronic lymphocytic leukemia. ( Abrisqueta, P; Bosch, F; Delgado, J; García-Marco, JA; Giraldo, P; González, M; Hernández-Rivas, JA; Jarque, I; Loscertales Pueyo, J; Martínez, R; Ramírez Payer, Á; Terol, MJ; Yáñez, L, 2017)
"The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology."	1.46	The regulation of tumor-suppressive microRNA, miR-126, in chronic lymphocytic leukemia. ( Andritsos, LA; Byrd, JC; Fabian, C; Flynn, JM; Guinn, D; Jaglowski, SM; Johnson, AJ; Jones, JA; Lehman, A; Maddocks, K; Woyach, JA; Yu, L, 2017)
"Central nervous system involvement from chronic lymphocytic leukemia (CLL) occurs infrequently, and manifestations include cognitive and cerebellar dysfunction and cranial nerve palsies."	1.43	Optic Neuropathy Due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy. ( Almarzouqi, SJ; Chevez-Barrios, P; Khan, K; Lee, AG; Malik, AI; Morgan, ML; Yalamanchili, S, 2016)
"Clinical responses to bendamustine in chronic lymphocytic leukemia (CLL) are highly heterogeneous and no specific markers to predict sensitivity to this drug have been reported."	1.43	CD69 expression potentially predicts response to bendamustine and its modulation by ibrutinib or idelalisib enhances cytotoxic effect in chronic lymphocytic leukemia. ( Arimany-Nardí, C; Aymerich, M; Cabezas, S; Campo, E; Clot, G; Colomer, D; Jiménez, L; Lee-Vergés, E; López-Guerra, M; López-Guillermo, A; Montraveta, A; Pastor-Anglada, M; Pérez-Galán, P; Pinyol, M; Roldán, J; Rosich, L; Roué, G; Villamor, N; Xargay-Torrent, S, 2016)
"A 70-year-old white man with stage C chronic lymphocytic leukemia who was being successfully treated with ibrutinib and rituximab developed bilateral, purpuric, painful cutaneous nodules."	1.43	Cutaneous, Purpuric Painful Nodules Upon Addition of Ibrutinib to RCVP Therapy in a CLL Patient: A Distinctive Reaction Pattern Reflecting Iatrogenic Th2 to Th1 Milieu Reversal. ( Magro, CM; Mulvey, JJ; Nuovo, GJ, 2016)
"Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015."	1.43	Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group. ( Andersson, PO; Asklid, A; Hansson, L; Karlsson, C; Karlsson, K; Lauri, B; Lundin, J; Mattsson, M; Norin, S; Österborg, A; Sandstedt, A; Winqvist, M, 2016)
" Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo."	1.42	Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy. ( Beurskens, FJ; Breij, EC; Da Roit, F; Engelberts, PJ; Golay, J; Gritti, G; Introna, M; Parren, PW; Rambaldi, A; Taylor, RP, 2015)
"Leukemic cells from Chronic Lymphocytic Leukemia (CLL) patients interact with stromal cells of the surrounding microenvironment."	1.42	Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival. ( Ave, E; Castelli, M; Chiodin, G; Facco, M; Frezzato, F; Gattazzo, C; Giorgi, CA; Lessi, F; Martini, V; Piazza, F; Semenzato, G; Severin, F; Trentin, L; Trimarco, V; Visentin, A; Zambello, R, 2015)
" Bruton's tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally bioavailable kinase inhibitor that has shown outstanding activity in CLL."	1.40	Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). ( Bojnik, E; Buggy, JJ; Byrd, JC; Chang, BY; Davis, ME; Dubovsky, JA; Efremov, DG; Gobessi, S; Goettl, VM; Harrington, BK; Johnson, AJ; Laurenti, L; MacMurray, J; Ruppert, AS; Smith, LL; Smucker, KA; Stefanovski, MR; Towns, WH; Woyach, JA, 2014)
"Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early."	1.40	Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. ( Byrd, JC; Clow, F; Flynn, J; Furman, RR; Ghia, E; James, DF; Johnson, AJ; Jones, J; Kipps, TJ; Lozanski, A; Lozanski, G; Lucas, D; Maddocks, K; Mantel, R; O'Brien, S; Rassenti, L; Ruppert, AS; Smith, LL; Smucker, K; Williams, K; Woyach, JA; Zhao, W; Zhong, Y, 2014)

Research

Studies (852)

Authors

Clinical Trials (75)

Trial Overview

Trial Outcomes

FD Cohort: Complete Response Rate (CRR; Complete Response/Complete Response With Incomplete Blood Count Recovery [CR/CRi]) Rate

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	4 (0.47)	29.6817
2010's	540 (63.38)	24.3611
2020's	308 (36.15)	2.80

Authors	Studies
Abdel-Qadir, H	1
Sabrie, N	1
Leong, D	1
Pang, A	1
Austin, PC	1
Prica, A	2
Nanthakumar, K	1
Calvillo-Argüelles, O	1
Lee, DS	1
Thavendiranathan, P	1
Abrisqueta, P	2
Loscertales, J	7
Terol, MJ	3
Ramírez Payer, Á	2
Ortiz, M	1
Pérez, I	1
Cuellar-García, C	2
Fernández de la Mata, M	1
Rodríguez, A	1
Lario, A	1
Delgado, J	8
Godoy, A	1
Arguiñano Pérez, JM	1
Berruezo, MJ	1
Oliveira, A	1
Hernández-Rivas, JÁ	3
García Malo, MD	1
Medina, Á	1
García Martin, P	1
Osorio, S	1
Baltasar, P	1
Fernández-Zarzoso, M	1
Marco, F	1
Vidal Manceñido, MJ	1
Smucler Simonovich, A	1
López Rubio, M	1
Jarque, I	2
Suarez, A	1
Fernández Álvarez, R	1
Lancharro Anchel, A	1
Ríos, E	1
Losada Castillo, MDC	1
Pérez Persona, E	1
García Muñoz, R	1
Ramos, R	1
Yáñez, L	2
Bello, JL	1
Loriente, C	1
Acha, D	1
Villanueva, M	1
Sivina, M	12
Kim, E	5
Wierda, WG	40
Ferrajoli, A	23
Jain, N	23
Thompson, P	7
Kantarjian, H	12
Keating, M	8
Burger, JA	57
Tedeschi, A	32
Frustaci, AM	8
Mauro, FR	22
Chiarenza, A	12
Coscia, M	16
Ciolli, S	5
Reda, G	17
Laurenti, L	24
Varettoni, M	6
Murru, R	10
Baratè, C	1
Sportoletti, P	11
Greco, A	1
Borella, C	2
Rossi, V	1
Deodato, M	6
Biagi, A	6
Zamprogna, G	4
Pelle, AC	1
Lapietra, G	1
Vitale, C	7
Morelli, F	4
Cassin, R	9
Fresa, A	2
Cavalloni, C	1
Postorino, M	4
Ielo, C	3
Cairoli, R	5
Di Raimondo, F	9
Montillo, M	13
Del Poeta, G	14
Yun, NK	1
Alrifai, T	1
Miller, IJ	1
Larson, ML	1
Kater, AP	19
Slinger, E	1
Cretenet, G	1
Martens, AW	1
Balasubramanian, S	6
Leverson, JD	1
Eldering, E	6
Rigolin, GM	14
Del Giudice, I	9
Bardi, A	2
Melandri, A	1
García-Jacobo, RE	1
Cura, F	1
Raponi, S	4
Ilari, C	3
Cafforio, L	3
Piciocchi, A	6
Arena, V	3
Albano, F	2
Molica, S	21
Trentin, L	21
Marchetti, M	7
Nanni, M	1
Peragine, N	5
Mariglia, P	4
Vignetti, M	3
Guarini, A	6
Foà, R	22
Cuneo, A	20
Allan, JN	10
Siddiqi, T	8
Kipps, TJ	29
Opat, S	3
Badoux, XC	1
Kuss, BJ	3
Jackson, S	2
Moreno, C	21
Jacobs, R	5
Pagel, JM	9
Flinn, I	1
Pak, Y	1
Zhou, C	11
Szafer-Glusman, E	2
Ninomoto, J	8
Dean, JP	11
James, DF	31
Ghia, P	27
Tam, CS	24
Akpinar, S	2
Dogu, MH	2
Celik, S	1
Ekinci, O	1
Hindilerden, IY	1
Dal, MS	2
Davulcu, EA	2
Tekinalp, A	1
Hindilerden, F	1
Ozcan, BG	1
Hacibekiroglu, T	1
Erkurt, MA	1
Bagci, M	1
Namdaroglu, S	1
Korkmaz, G	1
Bilgir, O	1
Cagliyan, GA	1
Ozturk, HBA	1
Serin, I	1
Tiryaki, TO	1
Ozatli, D	1
Korkmaz, S	1
Ulas, T	1
Eser, B	1
Turgut, B	2
Altuntas, F	2
Zimmerman, SM	1
Peer, CJ	1
Figg, WD	1
O'Brien, SM	15
Cappelli, LV	1
Soscia, R	1
De Propris, MS	3
Steingrímsson, V	2
Lund, SH	1
Dickman, PW	1
Weibull, CE	1
Björkholm, M	2
Landgren, O	2
Kristinsson, SY	2
Bloomquist, MS	1
Curry, JL	1
Krishnan, B	1
Rivero, G	1
Curry, CV	1
Diwan, AH	1
Teh, JSK	1
Tam, PCK	1
Badenoch, PR	1
Adamson, PJ	1
Brennan, C	1
Marshman, G	1
Gordon, DL	1
Langerbeins, P	7
Zhang, C	3
Robrecht, S	9
Cramer, P	16
Fürstenau, M	7
Al-Sawaf, O	6
von Tresckow, J	7
Fink, AM	9
Kreuzer, KA	5
Vehling-Kaiser, U	2
Tausch, E	8
Müller, L	3
Eckart, MJ	1
Schlag, R	1
Freier, W	1
Gaska, T	1
Balser, C	1
Reiser, M	1
Stauch, M	1
Wendtner, CM	13
Fischer, K	11
Stilgenbauer, S	23
Eichhorst, B	16
Hallek, M	26
Spaner, DE	6
Luo, Y	1
Wang, G	5
Gallagher, J	1
Tsui, H	3
Shi, Y	6
Wang, H	2
Tian, S	2
Zhao, Q	2
Blumenschein, W	1
Yearley, JH	1
Secreto, CR	2
Sinha, S	2
Call, TG	16
Wang, Y	8
Parikh, SA	17
Kenderian, SS	10
He, R	2
Leis, JF	16
Shi, M	4
Van Dyke, DL	6
Kay, NE	22
Slager, SL	14
Braggio, E	10
Yan, H	3
Ding, W	18
Davis, JE	1
Sharpe, C	1
Mason, K	1
Koldej, RM	1
Ritchie, DS	1
Bergman, P	1
Blennow, O	1
Hansson, L	4
Mielke, S	1
Nowak, P	1
Chen, P	2
Söderdahl, G	1
Österborg, A	11
Smith, CIE	2
Wullimann, D	1
Vesterbacka, J	1
Lindgren, G	1
Blixt, L	1
Friman, G	1
Wahren-Borgström, E	1
Nordlander, A	1
Gomez, AC	1
Akber, M	1
Valentini, D	1
Norlin, AC	1
Thalme, A	1
Bogdanovic, G	1
Muschiol, S	1
Nilsson, P	1
Hober, S	1
Loré, K	1
Chen, MS	1
Buggert, M	1
Ljunggren, HG	1
Ljungman, P	2
Aleman, S	1
Shanafelt, T	1
Wiestner, A	36
Li, J	8
Krigsfeld, G	2
Ahn, IE	10
Steele, L	1
George, C	1
Cerio, R	1
O'Toole, EA	1
Shah, HR	1
Stephens, DM	5
Visentin, A	15
Cibien, F	1
Pietrasanta, D	5
Gentile, M	15
Quaglia, FM	4
Scarfò, L	10
Pravato, S	2
Piazza, F	5
Naylor-Adamson, L	1
Chacko, AR	1
Booth, Z	1
Caserta, S	1
Jarvis, J	1
Khan, S	2
Hart, SP	1
Rivero, F	1
Allsup, DJ	2
Arman, M	1
Bories, P	1
Ysebaert, L	19
Aslan Candır, B	1
Yiğenoğlu, TN	1
Kızıl Çakar, M	1
Purroy, N	1
Tong, YE	1
Lemvigh, CK	1
Cieri, N	1
Li, S	2
Parry, EM	1
Zhang, W	3
Rassenti, LZ	4
Lesnick, C	1
Shanafelt, TD	16
Livak, KJ	2
Kharchenko, PV	1
Neuberg, DS	2
Olsen, LR	1
Fan, J	3
Gohil, SH	2
Wu, CJ	7
Greil, R	4
Demirkan, F	9
Anz, B	4
Larratt, L	3
Simkovic, M	5
Novak, J	2
Strugov, V	3
Gill, D	6
Gribben, JG	9
Kwei, K	1
Dai, S	5
Hsu, E	5
Flinn, IW	14
Tahir, F	1
Sy, J	1
Reddel, S	1
Trotman, J	1
Yavorkovsky, LL	1
Huber, H	1
Edenhofer, S	1
Schneider, C	2
Bloehdorn, J	2
Dreger, P	5
Ritgen, M	4
Illmer, T	4
Illert, AL	1
Dürig, J	2
Böttcher, S	5
Niemann, CU	17
Kneba, M	4
Döhner, H	3
Kumekawa, H	1
Watanabe, D	1
Tamura, K	1
Mizuchi, D	1
Egyed, M	1
Lueff, S	1
Borbely, J	1
Illes, A	2
Giannarelli, D	8
De Paoli, L	4
Moia, R	8
Levato, L	8
Giordano, A	1
Stelitano, C	1
Noto, A	3
Guarente, V	1
Gaidano, G	18
Foa', R	1
Ma, XY	1
Zhao, M	1
Li, YD	1
Chen, Y	6
Wei, L	1
Chen, ZS	1
Barr, PM	35
Bannerji, R	2
Russell, K	1
Wang, E	1
Mi, X	1
Thompson, MC	4
Montoya, S	1
Notti, RQ	1
Afaghani, J	1
Durham, BH	1
Penson, A	1
Witkowski, MT	1
Lu, SX	1
Bourcier, J	1
Hogg, SJ	1
Erickson, C	1
Cui, D	1
Cho, H	1
Singer, M	1
Totiger, TM	1
Chaudhry, S	1
Geyer, M	1
Alencar, A	1
Linley, AJ	1
Palomba, ML	3
Coombs, CC	2
Park, JH	3
Zelenetz, A	1
Roeker, L	3
Rosendahl, M	1
Tsai, DE	1
Ebata, K	1
Brandhuber, B	1
Hyman, DM	1
Aifantis, I	1
Mato, A	10
Taylor, J	1
Abdel-Wahab, O	1
Innocenti, I	10
Motta, M	2
Pennese, E	2
Rughini, A	1
Di Sevo, D	1
Tomasso, A	1
Autore, F	6
Pompili, M	2
Coutre, S	18
McKinney, M	1
Rogers, K	3
Mokatrin, A	2
Valentino, R	3
Szoke, A	3
Deshpande, S	1
Zhu, A	1
Arango-Hisijara, I	1
Osei-Bonsu, K	1
Wang, M	2
O'Brien, S	46
Karel, MFA	1
Tullemans, BME	1
D'Italia, G	1
Lemmens, TP	1
Claushuis, TAM	1
Kuijpers, MJE	1
Cosemans, JMEM	1
Collins, J	1
Stump, SE	1
Heiling, H	1
Muir, M	1
Deal, A	1
Proco, D	1
Nguyen, C	1
Cozad, M	1
Muluneh, B	1
Sorin, B	1
Vigneron, J	1
Fadlallah, J	1
Mondesir, J	1
Fieschi, C	1
Oksenhendler, E	1
Galicier, L	1
Malphettes, M	4
Angotzi, F	1
Scarmozzino, F	1
Cellini, A	1
Bertorelle, R	1
Pizzi, M	3
Binotto, G	1
Dei Tos, AP	1
Matutes, E	2
Polliack, A	13
Owen, C	9
Robak, T	15
Bairey, O	6
Hillmen, P	32
Coutre, SE	16
Dearden, C	5
Grosicki, S	8
McCarthy, H	4
Li, JY	3
Offner, F	3
Wang, XV	3
Hanson, CA	7
Paietta, EM	2
Barrientos, J	3
Jelinek, DF	2
Zhang, CC	3
Cashen, AF	3
Mato, AR	22
Singh, AK	3
Mullane, MP	3
Little, RF	4
Erba, H	5

Trial	Phase	Enrollment	Study Type	Start Date	Status
Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma[NCT02910583]	Phase 2	323 participants (Actual)	Interventional	2016-09-28	Active, not recruiting
A Placebo-Controlled, Double-Blind, Randomized, Multicenter, Three Arm Phase III Trial to Compare the Efficacy and Safety of Ibrutinib vs. Placebo in Previously Untreated Binet Stage A Chronic Lymphocytic Leukemia Patients With Risk of Early Disease Progr[NCT02863718]	Phase 3	515 participants (Actual)	Interventional	2014-04-30	Completed
Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Versus Chlorambucil in Patients 65 Years or Older With Treatment-naive Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma[NCT01722487]	Phase 3	269 participants (Actual)	Interventional	2013-03-31	Completed
A Randomized, Multi-center, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia o[NCT02264574]	Phase 3	229 participants (Actual)	Interventional	2014-10-06	Completed
A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)[NCT02048813]	Phase 3	529 participants (Actual)	Interventional	2014-02-20	Active, not recruiting
A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Need Therapy and Are Older Than 65 or Have a 17p Deletion[NCT01500733]	Phase 2	86 participants (Actual)	Interventional	2012-01-05	Active, not recruiting
An Open-label Extension Study in Patients 65 Years or Older With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib Versus Chlorambucil)[NCT01724346]	Phase 3	232 participants (Actual)	Interventional	2012-08-28	Completed
A Dose Escalation Study of Selinexor (KPT-330), a Selective Inhibitor of Nuclear Export, and Ibrutinib, a Bruton's Tyrosine Kinase Inhibitor, in Patients With Relapsed and Refractory Chronic Lymphocytic Leukemia or Aggressive Non-Hodgkin Lymphoma[NCT02303392]	Phase 1	34 participants (Actual)	Interventional	2015-03-11	Active, not recruiting
A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations[NCT03226301]	Phase 2	230 participants (Anticipated)	Interventional	2017-06-23	Active, not recruiting
Implanted Loop Recorders (ILR) for the Detection and Management of Arrhythmia in Patients Treated With Bruton Tyrosine Kinase (BTK) Inhibitors[NCT05643235]		50 participants (Anticipated)	Interventional	2022-11-01	Recruiting
A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma[NCT01578707]	Phase 3	391 participants (Actual)	Interventional	2012-06-30	Completed
Efficacy and Safety of Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma：a Single-center, Open-label, Pragmatic Clinical Trial[NCT05020392]	Phase 3	24 participants (Anticipated)	Interventional	2021-09-14	Recruiting
Prospective, Open-label, Multicentre Phase-II Trial to Evaluate Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by Ofatumumab and Ibrutinib Followed by Ibrutinib and Ofatumumab Maintenance in CLL Patients[NCT02689141]	Phase 2	66 participants (Actual)	Interventional	2016-02-04	Completed
A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma[NCT03734016]	Phase 3	652 participants (Actual)	Interventional	2018-11-01	Active, not recruiting
A Long-term Safety Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia[NCT01109069]	Phase 2	199 participants (Actual)	Interventional	2010-06-30	Completed
A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia[NCT01105247]	Phase 1/Phase 2	133 participants (Actual)	Interventional	2010-05-31	Completed
Real Life Assessment of the Association and Its Determinants Between Side Effects and Plasmatic Concentrations of Two Protein Kinase Inhibitors: Ibrutinib (IMBRUVICA®) and Idelalisib (ZYDELIG®) in Hematological Malignancies Treatment.[NCT02824159]		121 participants (Actual)	Observational	2016-04-30	Completed
A Phase 3 Multicenter, Randomized, Prospective, Open-label Trial of Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab Plus Venetoclax (RVe) Versus Obinutuzumab (GA101) Plus Venetoclax (GVe) Versus Obinutuzumab Plus Ibrutinib Plus Venetoclax (GIVe) in [NCT02950051]	Phase 3	926 participants (Actual)	Interventional	2016-12-13	Active, not recruiting
Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic[NCT01611090]	Phase 3	578 participants (Actual)	Interventional	2012-09-19	Completed
Obinutuzumab, Ibrutinib, and Venetoclax for Relapsed and Previously Untreated Chronic Lymphocytic Leukemia (CLL)[NCT02427451]	Phase 1/Phase 2	87 participants (Actual)	Interventional	2015-08-03	Active, not recruiting
A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects With B Cell Malignancy[NCT03301207]	Phase 1	25 participants (Actual)	Interventional	2017-10-20	Completed
A Phase I/II Trial of Ruxolitinib (Jakafi) in Patients With Chronic Lymphocytic Leukemia Who Are Unfit for Conventional First-line Therapy Due to Age or 17p Deletions[NCT02015208]	Phase 1/Phase 2	13 participants (Actual)	Interventional	2014-04-30	Completed
A Phase I/II Trial of Ruxolitinib in Chronic Lymphocytic Leukemia Patients at Risk for Progression on Ibrutinib[NCT02912754]	Phase 1/Phase 2	36 participants (Anticipated)	Interventional	2017-03-31	Not yet recruiting
"Phase II, Multicenter, Trial, Exploring Chemo-free Treatment (GA101+Ibrutinib) and MRD-driven Strategy in Previously Untreated Symptomatic B-chronic Lymphocytic Leukemia Medically Fit A Study From the Goelams/GCFLLC/MW Intergroup"[NCT02666898]	Phase 2	135 participants (Actual)	Interventional	2015-10-31	Completed
A Phase 3, Randomized, Study to Assess the Efficacy and Safety of Ublituximab in Combination With Ibrutinib Compared to Ibrutinib Alone, in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)[NCT02301156]	Phase 3	126 participants (Actual)	Interventional	2015-01-27	Completed
A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy[NCT02717611]	Phase 2	60 participants (Actual)	Interventional	2016-03-08	Active, not recruiting
A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 and Ibrutinib (BIG) Followed by GA101 and Ibrutinib Maintenance in CLL Patients (CLL2-BIG Protocol)[NCT02345863]	Phase 2	66 participants (Actual)	Interventional	2015-01-16	Completed
A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 and ABT-199 Followed by ABT-199 and GA101 Maintenance in CLL Patients[NCT02401503]	Phase 2	66 participants (Actual)	Interventional	2015-05-06	Active, not recruiting
A Phase II Study of Venetoclax and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL)[NCT02756897]	Phase 2	234 participants (Actual)	Interventional	2016-07-07	Active, not recruiting
A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)[NCT01886872]	Phase 3	547 participants (Actual)	Interventional	2013-12-09	Active, not recruiting
A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia[NCT02477696]	Phase 3	533 participants (Actual)	Interventional	2015-07-28	Active, not recruiting
Prospective Economic Analysis: A Randomized Phase III CLL Study of Bendamustine Plus Rituximab Versus Ibrutinib + Rituximab vs Ibrutinib Alone in Untreated Older Patients (≥65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)[NCT02414022]		55 participants (Actual)	Observational	2015-04-15	Active, not recruiting
Long-term Effect of Chronic Ibrutinib Therapy on Left Atrial Function[NCT03751410]		40 participants (Actual)	Observational [Patient Registry]	2018-12-01	Completed
A Phase II Study of Anti-PD-1 Antibody (MK-3475) in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Other Low Grade B Cell Non-Hodgkin Lymphoma (NHL)[NCT02332980]	Phase 2	65 participants (Actual)	Interventional	2015-02-19	Completed
A Phase 1/2, Multicenter, Open-label, and Dose-escalation Study of ACP-196 in Subjects With Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia[NCT02029443]	Phase 1/Phase 2	306 participants (Actual)	Interventional	2014-01-30	Active, not recruiting
A Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765(Ibrutinib), in Relapsed and Refractory Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and B-cell Prolymphocytic Leukemia (B-PLL)[NCT01589302]	Phase 2	154 participants (Actual)	Interventional	2012-05-21	Active, not recruiting
Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia[NCT00281983]	Phase 1/Phase 2	100 participants (Actual)	Interventional	2000-06-30	Completed
A Phase 2, Open Label Single Arm Study for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis[NCT03529955]	Phase 2	8 participants (Actual)	Interventional	2018-06-12	Completed
A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor Therapy[NCT02141282]	Phase 2	127 participants (Actual)	Interventional	2014-09-10	Completed
Treatment Patterns, Outcomes, and Patient-Reported Health-Related Quality of Life: A Prospective Disease Registry of Patients With Mantle Cell Lymphoma Treated With Novel Agents[NCT03816683]		229 participants (Actual)	Observational	2019-04-01	Active, not recruiting
A Multicenter Clinical Study of Orelabrutinib Combined With Lenalidomide and Rituximab (OR2) in the Treatment of Recurrent and Refractory CD20+ B-cell Lymphoma[NCT05014100]	Phase 2	55 participants (Anticipated)	Interventional	2021-09-01	Not yet recruiting
A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL[NCT02200848]	Phase 1	5 participants (Actual)	Interventional	2014-04-30	Terminated (stopped due to Recruitment difficulties and toxicity)
A Pilot Study of Different Doses of Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)[NCT02801578]	Phase 2/Phase 3	11 participants (Actual)	Interventional	2016-07-06	Completed
A Prospective Cohort of Obinutuzumab and Chlorambucil (GC) Chemotherapy for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia Including Next- Generation Sequencing (NGS)-Based Assessment[NCT04059081]	Phase 2	31 participants (Anticipated)	Interventional	2019-07-09	Recruiting
Ibrutinib vs Ibrutinib + Rituximab (i vs iR) in Patients With Relapsed (CLL)[NCT02007044]	Phase 2	208 participants (Anticipated)	Interventional	2013-12-06	Active, not recruiting
A Multi-center Phase I/Ib Study Evaluating the Efficacy and Safety of the Novel PI3k Delta Inhibitor TGR-1202 in Combination With Ibrutinib in Patients With Select B-Cell Malignancies[NCT02268851]	Phase 1	45 participants (Actual)	Interventional	2014-11-30	Active, not recruiting
A Phase 1/2a Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Subjects With Hematologic Malignancies[NCT02329847]	Phase 1/Phase 2	144 participants (Actual)	Interventional	2015-03-11	Completed
A Phase I/Ib Study Evaluating the Efficacy and Safety of Ublituximab, a Third-Generation Anti-CD20 Monoclonal Antibody, in Combination With TGR-1202, a Novel PI3k Delta Inhibitor; and Ibrutinib or Bendamustine, in Patients With B-cell Malignancies.[NCT02006485]	Phase 1	160 participants (Actual)	Interventional	2013-12-13	Completed
A Phase I/IIa Trial For The Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19[NCT00466531]	Phase 1/Phase 2	50 participants (Actual)	Interventional	2007-03-21	Active, not recruiting
A Phase 2 Study of MRD Adapted Therapy With Venetoclax-obinutuzumab in Patients With High or Intermediate BALL Risk Relapsed or Refractory CLL, With Addition of Acalabrutinib in Patients Who Fail to Achieve MRD Eradication[NCT04560322]	Phase 2	40 participants (Anticipated)	Interventional	2020-10-19	Recruiting
Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant[NCT03689894]	Phase 1/Phase 2	2 participants (Actual)	Interventional	2019-04-11	Terminated (stopped due to Insufficient accrual)
Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Early Stage CLL With High Risk of Early Disease Progression[NCT04178798]	Phase 3	22 participants (Actual)	Interventional	2019-12-09	Active, not recruiting
Phase Ib Dose Finding Study of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (MCL)[NCT02446236]	Phase 1	27 participants (Actual)	Interventional	2015-06-18	Active, not recruiting
Sequential Triple Therapy With Ibrutinib, Obinutuzumab and Venetoclax in First and Second Line for Patients With Chronic Lymphocytic Leukemia[NCT03755947]	Phase 2	3 participants (Actual)	Interventional	2018-12-01	Completed
Efficacy of BCR Inhibitors in the Treatment of Autoimmune Cytopenias Associated With Chronic Lymphocytic Leukemia (CLL): A Retrospective Analysis of the French Innovative Leukemia Organization (FILO)[NCT03469895]		40 participants (Actual)	Observational	2017-07-21	Active, not recruiting
Expression of CD19 Complex in Lymphoproliferative Disorders[NCT04734470]		92 participants (Anticipated)	Observational	2021-03-31	Not yet recruiting
A Phase 2 Study of the Combination of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 and Rituximab in High-Risk Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) Patients[NCT01520519]	Phase 2	40 participants (Actual)	Interventional	2012-02-27	Completed
Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma[NCT01236391]	Phase 2	115 participants (Actual)	Interventional	2011-02-28	Completed
Phase I Dose-Escalation Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma[NCT00849654]	Phase 1	66 participants (Actual)	Interventional	2009-02-28	Completed
A Phase 1 Dose-ranging Study to Investigate the Safety, Tolerability, and Pharmacokinetics of MRG-106 Following Local Intratumoral, Subcutaneous, and Intravenous Administration in Subjects With Various Lymphomas and Leukemias[NCT02580552]	Phase 1	66 participants (Actual)	Interventional	2016-02-09	Completed
Clinical Research for Efficacy and Safety of Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission[NCT05596097]	Phase 2	15 participants (Anticipated)	Interventional	2022-10-30	Not yet recruiting
Zanubrutinib in Relapsed or Refractory Warm Autoimmune Hemolytic Anemia: a Prospective Cohort Study[NCT05922839]	Phase 2	22 participants (Anticipated)	Interventional	2023-06-30	Not yet recruiting
An Open-Label, Sequential and 2-Way Crossover Pharmacokinetic Study to Assess the Absolute Bioavailability of Oral PCI-32765 and the Effect of Grapefruit Juice on the Bioavailability of PCI-32765 in Healthy Subjects[NCT01866033]	Phase 1	8 participants (Actual)	Interventional	2013-06-30	Completed
Open-Label, Randomized, 4-Way Crossover Study to Determine the Effect of Food on the Pharmacokinetics of PCI-32765[NCT01820936]	Phase 1	52 participants (Actual)	Interventional	2013-03-31	Completed
A Phase 1b, Multicenter, Open-label, Parallel-group Safety Study of a Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI 32765, in Combination With Chemotherapy in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma[NCT01292135]	Phase 1	33 participants (Actual)	Interventional	2011-02-28	Completed
An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia[NCT01217749]	Phase 1/Phase 2	71 participants (Actual)	Interventional	2010-12-31	Completed
Exploring Patient Experiences of Individuals Joining Chronic Lymphocytic Leukemia Clinical Trials[NCT05899543]		500 participants (Anticipated)	Observational	2024-07-31	Not yet recruiting
Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)[NCT01747486]	Phase 2	42 participants (Actual)	Interventional	2013-01-02	Completed
The Roles of Education and Patient Engagement to Improve Symptom Management and the Quality of Life for Patients With Chronic Lymphocytic Leukemia[NCT03231579]		85 participants (Actual)	Observational	2017-07-21	Completed
A Pilot Phase II Study Using Ibrutinib and Short-Course Fludarabine in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)[NCT02514083]	Phase 2	29 participants (Actual)	Interventional	2015-12-09	Active, not recruiting
A Phase 2 Study to Assess the Safety and Efficacy of TGR-1202 in Patients With Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK (Bruton Tyrosine Kinase) or PI3K-Delta (Phosphoinositide-3-kinase) Inhibitor Therapy[NCT02742090]	Phase 2	51 participants (Actual)	Interventional	2016-04-21	Completed
An Open-label, Single Arm, Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma With 17p Deletion (RESONATE™-17)[NCT01744691]	Phase 2	145 participants (Actual)	Interventional	2013-01-31	Completed
A Pilot Study to Determine the Effects of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)[NCT01752426]	Phase 1/Phase 2	30 participants (Actual)	Interventional	2012-12-17	Completed
A Phase I Study of Ibrutinib (PCI-32765) in Combination With Revlimid/Dexamethasone (Rd) in Relapsed/Refractory Multiple Myeloma[NCT03702725]	Phase 1	14 participants (Actual)	Interventional	2019-08-29	Active, not recruiting
Short-term Combined Acalabrutinib and Venetoclax Treatment of Newly Diagnosed Patients With CLL at High Risk of Infection and/or Early Treatment, Who do Not Fulfil IWCLL Treatment Criteria.[NCT03868722]	Phase 2/Phase 3	212 participants (Anticipated)	Interventional	2019-10-11	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

CR/CRi rate is defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2008 IWCLL criteria (halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD up to primary analysis data cutoff date of 15 December 2020. Median follow-up time was 27.9 months at the time of the primary analysis.

FD Cohort: DOR

Intervention	percentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated	55.9
FD Cohort: All Treated	55.3

Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of the median 27.9 months study follow-up, the Kaplan-Meier estimate of DOR at 24 months landmark time was presented. (NCT02910583)
Timeframe: From initial documentation of a response, until PD or death from any cause, whichever occurs first. Overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 December 2020).

FD Cohort: Kaplan-Meier Estimate of OS Rate at 24 Months Landmark Time

Intervention	percentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated	96.1
FD Cohort: All Treated	94.7

OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the median 38.2 months study follow-up, the Kaplan-Meier estimate of OS rate at 24 months landmark time was presented. (NCT02910583)
Timeframe: From the first dose of ibrutinib to time of death. Overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 December 2020).

FD Cohort: Kaplan-Meier Estimate of PFS Rate at 24 Months Landmark Time

Intervention	percentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated	97.7
FD Cohort: All Treated	98.1

PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the median 27.9 months study follow-up, the Kaplan-Meier estimate of PFS rate at 24 months landmark time was presented. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD or death. Overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 December 2020).

FD Cohort: ORR

Intervention	percentage of participants (Median)
FD Cohort, Non-Del 17p Population: All Treated	96.2
FD Cohort: All Treated	94.8

ORR is defined as the percentage of participants who achieve a best overall response CR, CRi, nPR, PR, or PRL as evaluated by investigator using 2008 IWCLL criteria (Halleck et al.). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD up to primary analysis data cutoff date of 15 December 2020. Median follow-up time was 27.9 months at the time of the primary analysis.

FD Cohort: TLS Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

Intervention	percentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated	95.6
FD Cohort: All Treated	96.2

TLS risk reduction was summarized by the percentage of participants with TLS risk reduced from high at baseline to medium or low after ibrutinib lead-in. A reduction in TLS risk from high risk to medium or low risk is clinically meaningful because there is a reduction in the extent of TLS monitoring and risk of hospitalization. TLS risk category is defined as the tumor burden category, where: Low=All lymph nodes (LN) < 5 cm AND absolute lymphocyte count (ALC) < 25 x 10^9/L; Medium=Any LN 5 cm to < 10 cm OR ALC ≥ 25 x 10^9/L; High=Any LN ≥ 10 cm OR ALC ≥ 25 x10^9/L AND any LN ≥ 5 cm. (NCT02910583)
Timeframe: Baseline, and last post-baseline value on or prior to venetoclax first dose date (cycle 4 day 1) or, for participants who never received venetoclax, the post-baseline value closest to cycle 4 day 1 (i.e. 84 days after the first dose date of ibrutinib).

MRD Cohort: 1-Year Disease-Free Survival (DFS) Rate in Confirmed uMRD Randomized Participants

Intervention	percentage of participants (Number)
FD Cohort: All Treated	94.1

DFS is defined as time from randomization date to MRD-positive relapse, or disease progression per investigator assessment (per 2008 International Workshop for Chronic Lymphocytic Leukemia [IWCLL] criteria [Halleck et al]) or death from any cause, whichever occurred first. 1-year DFS estimated using Kaplan-Meier method at 12 months landmark time. (NCT02910583)
Timeframe: 1 year after randomization

MRD Cohort: CRR (CR/CRi Rate)

Intervention	percentage of participants (Number)
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	95.3

CR/CRi rate is defined as the percentage of participants achieving a best overall response of CR or CRi per 2008 IWCLL criteria (Halleck et al.) on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurred earlier. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD (up to primary analysis data cutoff date of 15 December 2020). Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Duration of Response (DOR)

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	62.8
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	72.1
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	60.5
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	74.2
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	56.3

Duration of response was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2008 IWCLL response criteria (Halleck et al.) and defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, until disease progression (PD) or death from any cause, whichever occurred first. As the median DOR was not reached as of the median 38.2 months study follow-up, the Kaplan-Meier estimate of DOR at 36 months landmark time was presented. (NCT02910583)
Timeframe: From initial documentation of a response, until PD or death from any cause, whichever occurs first. Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Kaplan-Meier Estimate of Overall Survival (OS) Rate at 36 Months Landmark Time

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	94.7
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	95.3
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	96.7

OS is defined as the time from the first dose date of study treatment until date of death due to any cause. As the median OS was not reached as of the median 38.2 months study follow-up, the Kaplan-Meier estimate of OS rate at 36 months landmark time was presented. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD or death (up to primary analysis data cutoff date of 15 December 2020). Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Kaplan-Meier Estimate of Progression Free Survival (PFS) Rate at 36 Months Landmark Time

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	99.4
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	100.0

PFS was defined as time from the first dose date of study treatment until disease progression (PD) or death from any cause, whichever occurs first. Assessment of PD was conducted in accordance with the 2008 IWCLL criteria (Halleck et al). As the median PFS was not reached as of the median 38.2 months study follow-up, the Kaplan-Meier estimate of PFS rate at 36 months landmark time was presented. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD or death. Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Overall Response Rate (ORR)

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	95.6
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	95.3
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	96.7

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL) evaluated in accordance with the 2008 IWCLL criteria (Halleck et al). Participants who did not have any postbaseline response assessment were considered as non-responders. This table is based on response assessments performed on or prior to initiation of subsequent antineoplastic therapy or, if applicable, reintroduction of study treatment, whichever occurs earlier. Kaplan-Meier estimate. (NCT02910583)
Timeframe: From the first dose of ibrutinib to the first confirmed PD (up to primary analysis data cutoff date of 15 December 2020). Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Pharmacokinetics (PK) of Ibrutinib When Dosed in Combination With Venetoclax: Observed Maximum Concentration (Cmax)

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	97.0
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	100.0

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Apparent Total Clearance at Steady-State (CLss/F)

Intervention	ng/mL (Geometric Mean)
MRD Cohort: All Treated	88.5

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Terminal Elimination Rate Constant (λz)

Intervention	L/h (Geometric Mean)
MRD Cohort: All Treated	833

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: AUC0-24h

Intervention	1/h (Geometric Mean)
MRD Cohort: All Treated	0.132

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: CLss/F

Intervention	ng*h/mL (Geometric Mean)
MRD Cohort: All Treated	48993

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Cmax

Intervention	L/h (Geometric Mean)
MRD Cohort: All Treated	8.16

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Venetoclax When Dosed in Combination With Ibrutinib: Tmax

Intervention	ng/mL (Geometric Mean)
MRD Cohort: All Treated	3034

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: Tumor Lysis Syndrome (TLS) Risk Reduction Rate With 3-Cycle Ibrutinib Lead-In (Percentage of Participants No Longer High Risk After 3-cycle Lead-in)

Intervention	hours (Median)
MRD Cohort: All Treated	6.00

FD Cohort: MRR

Intervention	percentage of participants (Number)
MRD Cohort: All Treated	90.0

MRR is defined as the percentage of participants who achieve MRD-negativity in either peripheral blood (PB) or bone marrow (BM) and achieve confirmed clinical response PR or better per 2008 IWCLL criteria (Halleck et al.). MRD-negativity is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^4), as assessed by flow cytometry of a PB or BM aspirate sample. Confirmed MRD-negative response for randomization purposes requires MRD-negativity serially over at least 3 cycles, with negativity in both BM and PB. (NCT02910583)
Timeframe: From randomization date until before any reintroduced treatment. Overall median follow-up time was 27.9 months at the time of the primary analysis (data cutoff date: 15 December 2020).

FD Cohort: Percentage of Participants With TEAEs, Treatment-Emergent SAEs, and Discontinuations Due to TEAEs

Intervention	percentage of participants (Number)
	BM or PB	BM	PB
FD Cohort, Non-Del 17p Population: All Treated	78.7	61.8	76.5
FD Cohort: All Treated	78.6	59.7	76.7

An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug. (NCT02910583)
Timeframe: From first dose until 30 days following last dose of study drug (up to data cutoff date of 15 Dec 2020). Treatment duration for the FD cohort was 13.3 months for ibrutinib and 11.1 for venetoclax.

MRD Cohort: MRD-Negativity Rate (MRR)

Intervention	percentage of participants (Number)
	Any TEAE	Any Grade >=3 TEAE	Any Ibrutinib (Ibr)-Related TEAE	Any Grade >=3 Ibrutinib-Related TEAE	Any Venetoclax (Ven)-Related TEAE	Any Grade >=3 Venetoclax-Related TEAE	Any TEAE Leading to Ibr or Ven Discontinuation	Any TEAE Leading to Ibr or Ven Discontinuation: Ibr Only	Any TEAE Leading to Ibr or Ven Discontinuation: Ven Only	Any TEAE Leading to Ibr or Ven Discontinuation: Both Ibr and Ven	Any TEAE Leading to Ibr or Ven Dose Reduction	Any TEAE Leading to Ibr Only Dose Reduction	Any TEAE Leading to Ven Only Dose Reduction	Any TEAE Leading to Both Ibr and Ven Dose Reduction	Any SAE	Any Grade >= 3 SAE	Any SAE Related to Ibr or Ven	Any Ibr-related SAE	Any Ven-related SAE	Fatal TEAE	Major Hemorrhage TEAE	Grade >= 3 Major Hemorrhage TEAE	Major Hemorrhage SAE
FD Cohort: All Treated	99.4	62.3	92.5	44.7	84.3	44.7	5.0	3.1	0	1.9	20.8	5.7	11.3	3.8	22.6	19.5	13.2	11.3	8.2	0.6	1.9	1.3	1.3

"MRR is defined as the percentage of participants who achieve MRD-negativity in either peripheral blood (PB) or bone marrow (BM) and achieve confirmed clinical response PR or better per 2008 IWCLL criteria (Halleck et al.). MRD-negativity is defined as <1 CLL cell per 10,000 leukocytes (<1 x 10^4), as assessed by flow cytometry of a PB or BM aspirate sample. Confirmed MRD-negative response for randomization purposes requires MRD-negativity serially over at least 3 cycles, with negativity in both BM and PB.~This rate is calculated in the uMRD Not Confirmed randomized population during the period from randomization date and before any reintroduced treatment." (NCT02910583)
Timeframe: From randomization date until before any reintroduced treatment. Overall median follow-up time was 38.2 months at the time of the primary analysis (data cutoff date: 15 December 2020).

MRD Cohort: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs

Intervention	percentage of participants (Number)
	PB or BM	BM	PB
MRD Cohort: All Treated	81.1	76.8	79.3
MRD Cohort/uMRD Not Confirmed: All Participants	63.5	54.0	58.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	51.6	41.9	48.4
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	75.0	65.6	68.8

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires unplanned in-patient hospitalization >24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. Severity of events were graded according to the Common Terminology Criteria for Adverse Events version 4.03: mild=grade1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5. Causal relation of study drug and event was assessed as not related, unlikely, possibly or probably related to the study drug. (NCT02910583)
Timeframe: From first dose until 30 days following last dose of study drug (up to data cutoff date of 15 Dec 2020). Treatment duration for the MRD cohort was 28.7 months for ibrutinib and 15.4 for venetoclax.

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Area Under the Plasma Concentration-Time Curve (AUC) Over the Last 24-hour Dosing Interval (AUC0-24h); AUC From Time Zero to the Time of Last Quantifiable Concentration (AUClast)

Intervention	percentage of participants (Number)
	Any TEAE	Any Grade >=3 TEAE	Any Ibrutinib (Ibr)-Related TEAE	Any Grade >=3 Ibrutinib-Related TEAE	Any Venetoclax (Ven)-Related TEAE	Any Grade >=3 Venetoclax-Related TEAE	Any TEAE Leading to Ibr or Ven Discontinuation	Any TEAE Leading to Ibr or Ven Discontinuation: Ibr Only	Any TEAE Leading to Ibr or Ven Discontinuation: Ven Only	Any TEAE Leading to Ibr or Ven Discontinuation: Both Ibr and Ven	Any TEAE Leading to Ibr or Ven Dose Reduction	Any TEAE Leading to Ibr Only Dose Reduction	Any TEAE Leading to Ven Only Dose Reduction	Any TEAE Leading to Both Ibr and Ven Dose Reduction	Any SAE	Any Grade >= 3 SAE	Any SAE Related to Ibr or Ven	Any Ibr-related SAE	Any Ven-related SAE	Fatal TEAE	Major Hemorrhage TEAE	Grade >= 3 Major Hemorrhage TEAE	Major Hemorrhage SAE
MRD Cohort: All Treated	100.0	73.8	94.5	57.9	80.5	44.5	12.8	7.3	1.2	4.3	24.4	14.6	5.5	4.3	31.1	26.2	18.3	15.9	5.5	0.6	2.4	1.8	2.4
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)	100.0	79.1	93.0	55.8	86.0	51.2	4.7	2.3	2.3	0	20.9	14.0	4.7	2.3	27.9	25.6	16.3	11.6	4.7	0	2.3	2.3	2.3
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)	100.0	65.1	93.0	48.8	76.7	34.9	0	0	0	0	23.3	9.3	11.6	2.3	18.6	16.3	11.6	9.3	7.0	0	0	0	0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib	100.0	71.0	96.8	61.3	80.6	45.2	9.7	9.7	0	0	22.6	16.1	0	6.5	35.5	29.0	22.6	19.4	9.7	3.2	3.2	3.2	3.2
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax	100.0	75.0	93.8	62.5	96.9	56.3	12.5	3.1	0	9.4	31.3	21.9	3.1	6.3	37.5	28.1	18.8	18.8	3.1	0	6.3	3.1	6.3

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

MRD Cohort: PK of Ibrutinib When Dosed in Combination With Venetoclax: Time to Cmax (Tmax); Time of Last Measurable Concentration (Tlast); Terminal Elimination Half-Life (t1/2,Term)

Intervention	ng*h/mL (Geometric Mean)
	AUC0-24h	AUClast
MRD Cohort: All Treated	504	480

(NCT02910583)
Timeframe: Cycle 6 Day 1: predose, at dose, 1 h (±15 min), 2 h (±15 min), 4 h (±15 min), 6 h (±15 min), 8 h (±15 min)

ORR (Overall Response Rate)

Intervention	hours (Median)
	tmax	tlast	t1/2term
MRD Cohort: All Treated	2.00	24.0	5.30

ORR is defined as the proportion of subjects who achieved complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR per IRC assessment. Response criteria are as outlined in the International Workshop on CLL (iwCLL) 2008 criteria with the 2012 iwCLL modification stating that treatment-related lymphocytosis in the setting of improvement in other parameters was not considered as PD and the 2013 iwCLL clarification of criteria for a partial response to therapy. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Overall Survival (OS)

Intervention	percentage of participants (Number)
Ibrutinib	82.4
Chlorambucil	35.3

OS is calculated for all randomized subjects as the duration of time from the date of randomization to the date of death due to any cause or the date last known alive for subjects who were not known to have died at study closure. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

PFS (Progression Free Survival)

Intervention	Months (Median)
Ibrutinib	NA
Chlorambucil	NA

"The primary objective of this study was to evaluate the efficacy of Ibrutinib compared with Chlorambucil based on the independent review committee (IRC) assessment of PFS~Progressive disease according to 2008 IWCLL guidelines was defined as:~Group A~Lymphadenopathy, increase ≥50%~Hepatomegaly, increase ≥50%~Splenomegaly, increase ≥50%~Blood lymphocytes, increase ≥ 50% over baseline~Group B~Platelets counts, decrease of ≥ 50% from baseline secondary to CLL~Hemoglobin, decrease of > 2 g/dL from baseline secondary to CLL" (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Hemoglobin Improvement

Intervention	Months (Median)
Ibrutinib	NA
Chlorambucil	18.9

The proportion of subjects who achieved Hemoglobin >11 g/dL or increase ≥ 2 g/dL over baseline and persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Hemoglobin Improvement in Subjects With Baseline Anemia

Intervention	Percentage of Participants (Number)
Ibrutinib	45.6
Chlorambucil	20.3

In randomized subjects with baseline hemoglobin ≤ 11 g/dL, the proportion of subjects who achieved Hemoglobin >11 g/dL or increase ≥ 2 g/dL over baseline persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Platelet Improvement

Intervention	Percentage of Participants (Number)
Ibrutinib	84.3
Chlorambucil	45.5

The proportion of subjects who achieved platelet >100 x 10^9/L or increase ≥50% over baseline and persisted continuously for ≥56 days (8 weeks) without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with the cutoff date of 4 May 2015. The median follow-up time is 18 month.

Proportion of Sustained Platelet Improvement in Subjects With Baseline Thrombocytopenia

Intervention	Percentage of Participants (Number)
Ibrutinib	27.2
Chlorambucil	11.3

In randomized subjects with baseline platelet ≤ 100 x 10^9/L, the proportion of subjects who achieved platelet >100 x 10^9/L or increase ≥50% over baseline persisted continuously for ≥56 days (8 wee without blood transfusion or growth factors. (NCT01722487)
Timeframe: Analysis was conducted when 15 months had elapsed after the last subject was randomized with cutoff date of 4 May 2015. The median follow-up time is 18 month.

Final Analysis: ORR Based on Investigator Assessment

Intervention	Percentage of Participants (Number)
Ibrutinib	77.1
Chlorambucil	42.9

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified CR, CRi, nPR or PR per investigator assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate. (NCT02264574)
Timeframe: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48

Intervention	percentage of participants (Number)
IBR+OB	91.2
CLB+OB	81.0

"OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.~As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier point estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 48 [final analysis]) are presented." (NCT02264574)
Timeframe: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).

Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48

Intervention	percentage of participants (Number)
IBR+OB	80.5
CLB+OB	81.3

"PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.~As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented." (NCT02264574)
Timeframe: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).

Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48

Intervention	percentage of participants (Number)
IBR+OB	74.0
CLB+OB	22.0

"PFS was analyzed within the high-risk population of participants with del17p or TP53 mutation or del 11q or IGHV unmutated at baseline per central lab results. PFS was defined as time from the date randomization to the date of first investigator-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.~As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 48 months (that is, the estimated percentage of participants with progression-free survival at Month 48) are presented." (NCT02264574)
Timeframe: Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).

Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response

Intervention	percentage of participants (Number)
IBR+OB	70.3
CLB+OB	8.0

Percentage of participants who achieved MRD-negative response, defined as < 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders. (NCT02264574)
Timeframe: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: Rate of Sustained Hemoglobin Improvement

Intervention	percentage of participants (Number)
IBR+OB	24.8
CLB+OB	17.2

Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors. (NCT02264574)
Timeframe: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Final Analysis: Rate of Sustained Platelet Improvement

Intervention	percentage of participants (Number)
IBR+OB	44.2
CLB+OB	44.0

Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors. (NCT02264574)
Timeframe: Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment

Intervention	percentage of participants (Number)
IBR+OB	30.1
CLB+OB	14.7

ORR, defined as the percentage of participants achieving a best overall response of protocol-specified complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), or partial response (PR) per IRC assessment at or prior to initiation of subsequent antineoplastic therapy. Assessment of response included physical examination, radiographic imaging, and evaluation of blood and marrow (if applicable), evaluated in accordance with the IWCLL 2008 criteria (Halleck et al). CR, CRi, nPR, and PR required confirmation with 2 consecutive assessments that were at least 56 days apart and no use of blood supportive product and/or growth factor during this period. Kaplan-Meier estimate. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30

Intervention	percentage of participants (Number)
IBR+OB	88.5
CLB+OB	73.3

"OS, defined as the time from the date of randomization to the date of death from any cause. All deaths observed as the time of the analysis were considered as events. For participants who were not known to have died at the time of the analysis, OS data were censored at the date last known alive.~As the median OS was not reached in either treatment arm at the time of the analysis, Kaplan Meier landmark estimates of the OS rate (that is, the estimated percentage of participants still surviving at Month 30 [primary analysis]) are presented." (NCT02264574)
Timeframe: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).

Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30

Intervention	percentage of participants (Number)
IBR+OB	85.5
CLB+OB	84.9

"PFS was analyzed within the high-risk sub-population of participants with del17p or TP53 mutation or del 11q at baseline per central lab results. PFS was defined as time from the date randomization to the date of first IRC-confirmed PD or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the IWCLL 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of PD was not considered progressive disease.~As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented." (NCT02264574)
Timeframe: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).

Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30

Intervention	percentage of participants (Number)
IBR+OB	82.4
CLB+OB	14.1

"PFS was defined as time from the date randomization to the date of first IRC-confirmed disease progression (PD) or date of death due to any cause, whichever occurred first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. Assessment of PD was conducted in accordance with the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Halleck et al) with the modification that treatment-related lymphocytosis in the absence of other signs or symptoms of disease progression was not considered progressive disease.~The primary analysis was performed after observing 94 PFS events as pre-specified in the study protocol. As the median PFS was not reached in the experimental (IBR+OB) arm at the time of the analysis, Kaplan Meier landmark estimates of the PFS rate at 30 months (that is, the estimated percentage of participants with progression-free survival at Month 30) are presented." (NCT02264574)
Timeframe: Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).

Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)

Intervention	percentage of participants (Number)
IBR+OB	78.5
CLB+OB	31.1

Percentage of participants with EQ-5D-5L utility score increase ≥ 0.08 points over baseline at or prior to initiation of subsequent antineoplastic therapy. The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life, comprising 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the participant's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. Participants with missing EQ-5D-5L data were considered not achieving clinically meaningful improvement. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response

Intervention	percentage of participants (Number)
IBR+OB	54.9
CLB+OB	56.0

Percentage of participants who achieved MRD-negative response, defined as < 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate per central laboratory. MRD samples were collected before initiation of subsequent antineoplastic treatment and MRD status was reported by central lab within 5 days after collection date. Participants with missing MRD data were considered non-responders. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Sustained Hemoglobin Improvement

Intervention	percentage of participants (Number)
IBR+OB	20.4
CLB+OB	17.2

Percentage of participants with sustained hemoglobin improvement, defined as hemoglobin increase ≥ 2 g/dL over baseline continuously for ≥ 56 days without blood transfusions or growth factors. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Sustained Platelet Improvement

Percentage of participants with platelet counts increase ≥ 50% over baseline continuously for ≥ 56 days without blood transfusion or growth factors. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Primary Analysis: Rate of Grade ≥ 3 or Serious Infusion-Related Reaction (IRR) Adverse Events

Percentage of participants experiencing grade ≥ 3 (severe or life threatening) or serious IRR adverse events that started on the day of an obinutuzumab infusion and were assessed as related or possibly related to obinutuzumab. Categories included those events with the Medical Dictionary for Regulatory Activities (MedDRA) dictionary preferred term of IRR and those events which are among the customized standardized MedDRA query (SMQ) for IRR. (NCT02264574)
Timeframe: Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).

Overall Survival (OS) Rate at 3 Years

Overall survival was defined as time from randomization to death from any cause or date last known alive. Overall survival rate at 3 years was estimated using the method of Kaplan-Meier. (NCT02048813)
Timeframe: Assessed every 3 months until progression; after progression, assessed every 3 months for first 2 years, every 6 months for years 3-5, up to 4 years and 8 months

Progression-free Survival (PFS) Rate at 3 Years

"PFS was defined as the time from randomization to CLL progression or death, whichever occurred first. Progression is characterized by any of the following:~≥ 50% increase from nadir since start of treatment (tx) in the sum of the products of at least 2 lymph nodes on 2 consecutive examinations 2 weeks apart~≥ 50% increase from nadir since start of tx in the size of liver and/or spleen~≥ 50% increase in the absolute number of circulating lymphocytes not due to tumor flare reaction. The absolute lymphocyte count must be ≥ 5x10^9/L to qualify as disease progression.~Transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with > 55% prolymphocytes). For patients who achieve a complete response or nodular partial response, progression is defined as recurrence of circulating leukemia cell clone in the peripheral blood and an absolute lymphocyte count > 5x10^9/L and/or recurrence of palpable lymphadenopathy > 1.5 cm by physical exam." (NCT02048813)
Timeframe: Assessed every 3 months until progression up to 4 years and 8 months

Overall Response Rate at 6 Months

"The primary endpoint was response after 6 cycles of therapy. Overall response rate was calculated as complete response plus partial response, based on the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2008 criteria.as follows:~Complete response (CR): all group A and group B criteria are met~Group A criteria: resolution of enlarged lymph nodes, normal size spleen and liver, absolute lymphocyte count < 4,000/uL, normocellular bone marrow with < 30% lymphocytes without nodules~Group B criteria: improved blood count (platelet count > 100,000/uL, hemoglobin > 11.0 g/dL, neutrophils > 1,500/uL)~Partial response (PR): at least 2 of the group A criteria plus one of the group B criteria are met~Group A criteria: >=50% decrease in target lymph nodes, >=50% decrease in spleen size, >=50% decrease in liver size, 50% reduction in marrow infiltrates~Group B criteria: platelet count > 100,000/uL, hemoglobin > 11.0 g/dL, neutrophils > 1,500/uL" (NCT01500733)
Timeframe: 6 months

OS (Overall Survival)

OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm (NCT01578707)
Timeframe: OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up

Overall Response Rate (ORR) by Independent Review Committee (IRC)

Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013 (NCT01578707)
Timeframe: About 18 months after the first subject was enrolled

Overall Response Rate (ORR) by Investigator

Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013

The primary objective of this study was to evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) according to 2008 IWCLL guidelines. (NCT01578707)
Timeframe: Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.

Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up

Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

Rate of Sustained Hemoglobin and Platelet Improvement

Proportion of subjects with hemoglobin (HgB) increase >=20 g/L and platelet (PLT) increase >=50% over baseline continuously for >=56 days without blood transfusions or growth factors. (NCT01578707)
Timeframe: From study initiation to study closure, including up to 6 years of study follow-up

ORR as Determined by Independent Review Committee (IRC)

"ORR is the percentage of participants with PR or higher, (CR/CRi) + PR + nodular PR per IRC assessment using the modified 2008 IWCLL guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for NHL for participants with SLL" (NCT03734016)
Timeframe: Up to approximately 3 years and 9 months

Overall Response Rate (ORR) as Determined by Investigator Assessment

"ORR is percentage of participants with partial response (PR) or higher, (defined as Complete response/ Complete response with incomplete bone marrow recovery (CR/CRi) + PR + nodular PR) per investigator assessment using the modified 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for non-Hodgkin lymphoma (NHL)) for participants with Small lymphocytic lymphoma (SLL)" (NCT03734016)
Timeframe: Up to approximately 3 years and 9 months

Death Event

All death events are due to AE, progressive disease, and other reasons. (NCT01109069)
Timeframe: 30 days after last dose of study drug

Number of Subjects With Adverse Events

Subjects were to receive ibrutinib once daily at the dose level the subject was receiving in the parent study until disease progression or unacceptable toxicity. The study included Screening, Treatment (from the first dose until study drug discontinuation), and Follow-up Phases. (NCT01109069)
Timeframe: 30 days after last dose of study drug, continue up to 6 months

Progressive Disease (PD)

A progressive disease confirmed by a CT scan. (NCT01109069)
Timeframe: 30 days after last dose of study drug, continue up to 6 months

Food Effect Cohort Assessments

Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose. (NCT01105247)
Timeframe: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.

Number of Participants With Treatment Emergent Adverse Events (AEs)

Number of participants who had experienced at least one treatment emergent AEs. (NCT01105247)
Timeframe: From first dose to within 30 days of last dose of PCI-32765

Percentage of Participants Achieving Response

Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. (NCT01105247)
Timeframe: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

Progression Free Survival Rate at 24 Months

Change From Baseline in Beta2 Microglobulin at End of Treatment (EOT)

Change from baseline in beta2 microglobulin at end of treatment at time of primary analysis was reported. (NCT01611090)
Timeframe: Baseline to EOT (Up to 2 years)

Change From Baseline in EORTC QLQ-C30 Physical Functioning Score at End of Treatment

"EORTC QLQ-C30 Physical Functioning Score is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from 1 = not at all to 4 = very much. Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which was rated on a 7-point scale ranging from 1 = very poor to 7 = excellent. Lower scores indicate worsening. All scale and item scores were linearly transformed to be in range from 0-100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms." (NCT01611090)
Timeframe: Baseline to EOT (up to 2 years)

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Utility Score Scale at End of Treatment

The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1. High score indicating a high level of utility. (NCT01611090)
Timeframe: Baseline to EOT (up to 2 years)

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale at End of Treatment

The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). (NCT01611090)
Timeframe: Baseline to EOT (up to 2 years)

Change From Baseline in FACIT-Fatigue Scale at End of Treatment

FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). (NCT01611090)
Timeframe: Baseline to EOT (up to 2 years)

Median Time to Clinically Meaningful Improvement in FACIT-Fatigue Scale

Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). (NCT01611090)
Timeframe: Up to 2 years

Number of Participants Who Received Subsequent Antineoplastic Therapy

Number of participants who received subsequent antineoplastic therapy was reported. (NCT01611090)
Timeframe: Up to 5 years

Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms

The disease-related symptoms included fatigue, weight loss, fevers, night sweats, abdominal discomfort/splenomegaly and anorexia. (NCT01611090)
Timeframe: From the date of randomization to disease progression (Up to 2 years)

Overall Response Rate (ORR)

ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR-2 of the following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum products of up to 6 lymph nodes, >=50% decrease in enlargement of spleen or liver; and 1 of the following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; no new enlarged nodes or new hepatosplenomegaly. (NCT01611090)
Timeframe: Up to 5 years

Overall Survival (OS)

OS was defined as the interval between the date of randomization and the date of death from any cause. (NCT01611090)
Timeframe: Up to 5 years

Percentage of Participants With Minimal Residual Disease (MRD)-Negative Response

MRD-negative response was defined as the percentage of participants who reach MRD negative disease status (less than 1 chronic lymphocytic leukemia [CLL] cell per 10,000 leukocytes) in either bone marrow or peripheral blood. All randomized participants were included in this analysis. Participants with missing MRD data were considered non-responders. (NCT01611090)
Timeframe: Up to 5 years

Progression-free Survival (PFS)

PFS was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. IWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other new organ infiltrates, bone lesion, ascites, or pleural effusion confirmed due to chronic lymphocytic leukemia (CLL); >=50% increase in existing lymph nodes; >=50% increase in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) or >=50% increase from nadir count confirmed on >=2 serial assessments if absolute lymphocyte count (ALC) >=30,000 per microliter and lymphocyte doubling time is rapid, unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b [Hgb] or platelets) attributable to CLL; and transformation to a more aggressive histology. (NCT01611090)
Timeframe: Up to 5 years

Change From Baseline in EORTC QLQ-CLL 16 Domain Scores at End of Treatment

The EORTC QLQ-CLL 16 is a 16-item disease specific module that comprises 5 domains of patient-reported health status important in CLL. There are three multi-item scales that include fatigue (2 items), treatment side effects and disease symptoms (8 items), and infection (4 items), and 2 single-item scales on social activities and future health worries. Responses are measured on a 4 point scale ranging from 1 (not at all) to 4 (very much). (NCT01611090)
Timeframe: Baseline to EOT (up to 2 years)

Percentage of Participants With Sustained Hematologic Improvement

Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (>)100* 109/liter (L) if baseline less than or equal to (<=) 100*109/L or increase >= 50 percent (%) over baseline; 2) Hemoglobin >11 gram per deciliters (g/dL) if baseline <= 11 g/dL or increase >= 2 g/dL over baseline. (NCT01611090)
Timeframe: Up to 5 years

Complete Response (CR) Rate

The CR rate was defined as the percentage of participants who achieved CR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. (NCT02301156)
Timeframe: Up to 62 months

Duration of Response (DOR)

DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC<4x10^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC>1.5x10^9/L,Platelets≥100x10^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC<4x10^9/L,>=50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC>1.5x10^9/L,Platelets>100x10^9/L,Hgb>110 g/L or >=50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of >50% in platelets/>20g/L in Hgb from highest on-study count. (NCT02301156)
Timeframe: From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months

Minimum Residual Disease (MRD) Negativity Rate

MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow. (NCT02301156)
Timeframe: Up to 62 months

Overall Response Rate (ORR)

ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)>1.5x10^9/L,platelets≥100x10^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC<4x10^9/L or >=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC>1.5x10^9/L,platelets>100x10^9/L,Hgb>110g/L or >=50% increase over baseline in any of these. (NCT02301156)
Timeframe: Up to 62 months

Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related. (NCT02301156)
Timeframe: From the first dose up to 30 days after the last dose of study drug (up to 57.3 months)

Progression-Free Survival (PFS)

PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: New nodes >1.5 cm in the LD and >1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb. (NCT02301156)
Timeframe: From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months

Time to Response (TTR)

TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC<4 x 10^9/L or >=50% decrease from baseline in SPD of target nodal lesions; splenomegaly; hepatomegaly; >=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; and Response in 1 of the following: ANC>1.5 x 10^9/L, platelets>100 x 10^9/L, Hgb>110 g/L or >=50% increase over baseline in any of these. (NCT02301156)
Timeframe: From the randomization up to 62 months

Duration of Response

"The duration of response of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.~DOR is calculated as date of disease progression or death (censoring date for censored subjects) - date of achieving the first CR, CRi, nPR, or PR + 1." (NCT02717611)
Timeframe: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Overall Survival

The overall survival of ACP-319 (acalabrutinib) in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy (NCT02717611)
Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

Progression-Free Survival

"The progression-free survival of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.~PFS is calculated as date of disease progression or death (censoring date for censored subjects) - first dose date + 1." (NCT02717611)
Timeframe: From the date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years).

The Overall Response Rate (ORR) of ACP-196 (Acalabrutinib)

"The overall response rate (ORR) of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.~ORR is defined as the proportion of subjects achieving a best overall response (BOR) of either complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) at or before initiation of subsequent anticancer therapy. ORR will be analyzed per investigator's assessment." (NCT02717611)
Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 4 years and 7 months). 1 cycle = 28 days

Time-to-Next Treatment

"The time to next treatment of ACP-196 (acalabrutinib) in subjects with relapsed / refractory CLL who are intolerant of ibrutinib therapy.~TTNT is defined as the time from date of first acalabrutinib treatment to date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever comes first. Subjects who do not have the above specified events prior to the data cutoff date will be censored at the date of last visit. TTNT will be calculated as follows:~(Earlier date of institution of subsequent anticancer therapy for CLL or date of death due to any cause) - date of first dose + 1. For censored subjects, date of last visit will replace earlier date of use of subsequent anticancer therapy for CLL or date of death due to any cause in the calculation." (NCT02717611)
Timeframe: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)

Duration of Response (DOR) (Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL)

The Kaplan-Meier method will be used to estimate median DOR. DOR is the time from first objective status to progression or death. CR requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly/splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate & biopsy must be normocellular for age. PR requires >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). PR with the exception of having less than a 50% reduction in peripheral lymphocyte count will be considered a PR except persistent lymphocytosis (PRL). (NCT01886872)
Timeframe: From the date of first response until progression or death, performed at 2.5 years after the last patient enrolled; up to 4 years.

Overall Survival (OS) at 2 Years

The Kaplan-Meier method will be used to estimate the rate of overall survival at 2 years in each treatment arm. OS will be measured from the date of registration to the date of the event (i.e., death) or the date of last follow-up to evaluate that event. Patients who are event-free at their last follow-up evaluation will be censored at that time point. (NCT01886872)
Timeframe: From the date of registration to the date of death, assessed up to 2 years

Percentage of Patients Achieving a Biopsy-proven Complete Response (CR)

Complete response (CR) requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Complete response rate and corresponding exact binomial 95% confidence intervals provided. (NCT01886872)
Timeframe: Performed at 2.5 years after the last patient enrolled; up to 4 years.

Percentage of Patients Achieving Any Response to Treatment (Overall Response Rate [ORR] [Complete Response [CR], CCR, Nodular Partial Response [nPR], Partial Response [PR], and PRL])

Complete response (CR) requires all of the following: absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly/splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate & biopsy must be normocellular for age. Partial response (PR) requires >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). PR with the exception of having less than a 50% reduction in peripheral lymphocyte count will be considered a PR except persistent lymphocytosis (PRL).Overall response rate and corresponding exact binomial 95% CI provided. (NCT01886872)
Timeframe: Performed at 2.5 years after the last patient enrolled;up to 4 years.

Percentage of Patients Achieving Complete (CR and CCR) or Nodular Partial Response (nPR)

Complete response (CR) requires all of the following: absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly on physical exam, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). CR with exception of not having a bone marrow biopsy performed will be considered a clinical CR (CCR). Response rate and corresponding exact binomial 95% confidence intervals provided. (NCT01886872)
Timeframe: Performed at 2.5 years after the last patient enrolled; up to 4 years.

Percentage of Patients Who Attain Minimal Residual Disease (MRD) Negative Status

Estimated using the number of patients who achieve minimal residual disease divided by the total number randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for MRD rates will be calculated. (NCT01886872)
Timeframe: Cycle 9 Day 1 Evaluation

Progression Free Survival (PFS)

The Kaplan-Meier method will be used to estimate the progression free survival distributions for each arm, with median estimates provided. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50% with >= 5000 B lymphocytes/mL in patients on Arm A or those on Arms 2 or 3 no longer receiving ibrutinib, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first. (NCT01886872)
Timeframe: Time from study entry to the time of documented disease progression or death. The analysis was event driven, performed at 2.5 years after the last patient enrolled;up to 4 years.

Progression Free Survival (PFS) Rate at 2 Years

The Kaplan-Meier method will be used to estimate the rate of progression free survival at 2 years in each treatment arm. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first. (NCT01886872)
Timeframe: Time from study entry to the time of documented disease progression or death, assessed up to 2 years

The Rate of Grade 3, 4, or 5 Treatment-related Non-hematologic Adverse Events (Toxicities)

The rate of grade 3, 4, or 5 treatment-related non-hematologic adverse events (toxicities) by arm; excludes adverse events occurring post-crossover for patients in Arm A (NCT01886872)
Timeframe: Performed at 2.5 years after the last patient enrolled; up to 4 years.

Number of Participants With Treatment-emergent Atrial Fibrillation

Number of participants with treatment-emergent atrial fibrillation (including atrial flutter) are reported. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Number of Participants With Treatment-emergent Infections Grade >= 3

Number of participants with treatment-emergent infections Grade >=3 are reported. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Number of Participants With Treatment-emergent Richter's Transformation

Richter's transformation is defined as the occurrence of an aggressive lymphoma in participants with a previous or concomitant diagnosis of CLL. Richter's transformation was assessed by central pathology. Number of participants with treatment-emergent Richter's transformation are reported. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Overall Survival (OS)

The OS is defined as the time from date of randomization to date of death due to any cause. The OS is assessed using the Kaplan-Meier method. (NCT02477696)
Timeframe: Baseline (Days -28 to -1) through 83.7 months (maximum observed duration)

Percentage of Participants With Lymphocytosis

Percentage of participants with at least one occurrence of treatment-related lymphocytosis defined as an elevation in ALC of >= 50% compared with baseline and a postbaseline assessment of > 5000/μL in the peripheral blood are reported. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Progression-free Survival (PFS) Based on Independent Review Committee (IRC) Assessment

The PFS is defined as the time from date of randomization to the date of first IRC-assessed PD or death due to any cause, whichever occurred first. PD (per International Workshop on Chronic Lymphocytic Leukemia [iwCLL] 2008 criteria): Lymphocytes >= 50% increase over baseline, or >= 50% increase in lymphadenopathy/hepatomegaly/splenomegaly, or >= 50% platelets or > 2 g/dL hemoglobin decreases from baseline secondary to chronic lymphocytic leukemia (CLL). The PFS is assessed using the Kaplan-Meier method. (NCT02477696)
Timeframe: Baseline (Days -28 to -1) through 55.2 months (maximum observed duration)

Number of Participants With Abnormal Vital Signs Reported as TEAEs

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, heart rate, and respiratory rate). (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Number of Participants With Electrocardiogram (ECG) Abnormality at Baseline

Number of participants with ECG abnormality at baseline are reported. (NCT02477696)
Timeframe: Baseline (Days -28 to -1)

Number of Participants With Shift From Baseline to Worst (Grade 3 and 4) Postbaseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

The ECOG performance status assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=death. Number of participants with shift from baseline (Days -28 to -1) to worst Grade 3 and 4 in ECOG performance status are reported. (NCT02477696)
Timeframe: Baseline (Days -28 to -1) through 83.5 months (maximum observed duration)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Number of Participants With Treatment-emergent Laboratory Abnormalities

Number of participants with treatment-emergent laboratory abnormalities are reported. Laboratory abnormality is defined as any abnormal finding during analysis of hematology and serum chemistry. (NCT02477696)
Timeframe: Day 1 through 83.5 months (maximum observed duration)

Complete Response Rate

Will be defined as complete response or incomplete blood count recovery. Estimated by the number of patients who achieve an incomplete blood count recovery or complete response divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true complete response rate will be calculated in each arm. (NCT02332980)
Timeframe: 1 year

Confirmed All Response Rate of Patients Treated With Combination Therapy

Confirmed response rate will be estimated by the number of patients with an objective status of complete response, incomplete blood count recovery, nodular partial response, clinical complete response or partial response while on the combination therapy divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate to the combination will be calculated. In addition, the responders on this study will be further examined in an exploratory manner to determine if there are any patterns in prognostic factors or disease characteristics, including whether the patient had a Richter's transformation or ibrutinib-resistant disease, for both single agent pembrolizumab and combination therapy responders. (NCT02332980)
Timeframe: 1 year

Duration of Response

The distribution of duration of response will be estimated using the method of Kaplan-Meier. Duration of response (DR) is defined for all evaluable patients who have achieved a PR, nPR, CCR, CRi, or CR (Arms A and B) or PMR, CMR, PR or CR (Arm C) as the date at which the patient's objective status is first noted to be a PR, nPR, CCR, CRi, or CR (Arms A and B) or PMR, CMR, PR or CR (Arm C) to the earliest date relapse is documented. (NCT02332980)
Timeframe: 5 years

Incidence of Adverse Events

Will be measured per National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Adverse events will be evaluated for single-agent pembrolizumab in each arm and also for the combination of pembrolizumab and the signal inhibitor in Arm A and Arm C. This outcome is reported in the adverse events section of this report. (NCT02332980)
Timeframe: 1 year

Overall Survival

The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Progression-free Survival of Patients Treated in Single Agent Phase

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02332980)
Timeframe: 5 years

Progression-free Survival of Patients Treated With Combination Therapy

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02332980)
Timeframe: 5 years

Proportion of Patients Who Achieve a Confirmed Response

Confirmed response is defined to be a partial response, nodular partial response, clinical complete response, confirmed response with incomplete blood count recovery or confirmed response (Arm A and B), or complete metabolic response, partial metabolic response, partial response, or confirmed response (Arm C). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated. (NCT02332980)
Timeframe: 1 year

Time to Next Treatment for Patients on Combination Therapy

The distribution of time to next treatment will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Time to Next Treatment for Patients Treated With Single-agent Pembrolizumab

The distribution of time to next treatment will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Treatment-free Survival of Patients Treated With Combination Therapy

The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Treatment-free Survival of Patients Treated With Single-agent Pembrolizumab

The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier. (NCT02332980)
Timeframe: 5 years

Duration of Response (DOR) as Assessed by the Investigator

The DoR is defined as the time from the date of achieving the first CR, CRi, or PR to the date of progressive disease (PD) or death due to any cause, whichever occurred first. The CR, CRi, or PR are defined in the above outcome measure. For CLL/SLL, PD is defined as lympho >=50% increase from baseline with >= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or >= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of >=50% from baseline secondary to CLL or < 100,000/µL and worsening bone marrow or Hb decrease of > 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The DoR was estimated using Kaplan-Meier method. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1

Participants with DLTs in Phase 1 are reported. The DLT was defined as any of the following events unless the adverse event is clearly related to disease progression or the participant's current medical history and associated comorbidities: (1) Any Grade 3 or greater nonhematologic toxicity with the exceptions of alopecia and Grade 3 nausea, vomiting, and diarrhea that respond to supportive therapy; (2) Hematologic toxicities including Grade 4 neutropenia lasting more than 5 days, Grade 4 or Grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion, Grade 3 or greater febrile neutropenia (body temperature of 38.5 degrees Celsius or more), or Grade 4 anemia, unexplained by underlying disease; or (3) Dosing delay due to toxicity for > 7 consecutive days. (NCT02029443)
Timeframe: From Day 1 to Day 28 after first dose of study drug

Percentage of Participants With Objective Response (OR) as Assessed by the Investigator

For CLL/SLL, OR is defined as complete remission (CR), CR with incomplete marrow recovery (CRi), or partial remission (PR). CR: lymphocytes (lympho) <4×10^9/L, normocellular bone marrow (BM), normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophil count (ANC) >1.5×10^9/L, platelets >100×10^9/L, hemoglobin (Hb) >11g/dL. Cri: lympho <4×10^9/L, hypocellular BM, NLN, L/S, persistent anemia, hrombocytopenia, or neutropenia. PR: >=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (<5×10^9/L or >=50% decrease from baseline) and criteria of ANC/platelets/Hb per CR or >=50% improvement over baseline. Hematology result were without exogenous growth factors/transfusion. For RS, OR as CR or PR by Cheson et al. 2014 based on PET/CT scans and bone marrow. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms and PR: >=50% decrease in sum of the product diameter of 6 largest nodal masses and no new sites of disease. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Progression Free Survival (PFS) as Assessed by the Investigator

The PFS is defined as the time from the date of first dose of study drug to the date of first PD or death due to any cause, whichever occurred first. For CLL/SLL, PD is defined as lympho >= 50 % increase from baseline with >= 5000 B lymphocytes/µL, progressive cytopenias by bone marrow biopsy, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or >= 50 % increase in lymphadenopathy/hepatomegaly/splenomegaly, platelets decrease of >= 50 % from baseline secondary to CLL or < 100,000/µL and worsening bone marrow or Hb decrease of > 2 g/dL from baseline secondary to CLL or decrease to less than 100 g/L and worsening bone marrow. For RS, PD is defined as an increase by 25 % in longest diameter, new lesion or assessable disease progression. The PFS was estimated using Kaplan-Meier method. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Apparent Oral Clearance (CL/F) of Acalabrutinib

The CL/F of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Apparent Volume of Distribution (Vz/F) of Acalabrutinib

The Vz/F of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib

The AUC0-6 of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib

The AUC0-inf of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Acalabrutinib

The AUC0-last of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib

The Cmax of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Number of Participants With Clinically Abnormal Vital Signs Reported as TEAEs

Participants with clinically abnormal vital signs (blood pressure, respiratory rate, pulse rate, or body temperature) reported as TEAEs are reported. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Clinically Important Laboratory Abnormalities With Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or More

Participants with clinically important laboratory abnormalities with CTCAE Grade 3 or more are reported. Laboratory analysis included hematology, clinical chemistry, amylase, lipase, cardiac troponin I, hepatitis B and C testing, and urinalysis. The CTCAE version 4.03 is a descriptive terminology is used for AE reporting. The CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Number of Participants With Treatment Emergent Events of Clinical Interest (ECI)

The treatment emergent ECI included the events identified based on preclinical findings, emerging data from clinical studies relating to acalabrutinib, and pharmacological effects of approved Bruton's tyrosine kinase (BTK) inhibitors and reported after the first dose of the study drug. (NCT02029443)
Timeframe: Day 1 through the final data cutoff date (approximately 7 years 6 months)

Terminal Elimination Half-life (t1/2) of Acalabrutinib

The t1/2 of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Terminal Elimination Rate Constant (λz) of Acalabrutinib

The λz of acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Time of Maximum Plasma Concentration (Tmax) of Acalabrutinib

The Tmax of Acalabrutinib is reported. (NCT02029443)
Timeframe: Predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on Day 1 and Day 8

Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R)

Cancer-Specific Stress was measured by the Impact of Event Scale-Revised Participants rated the intensity of these feelings using a five-point Likert scale ranging from 0=not at all to 4=extremely. Patients rated the frequency of their feelings or events for the previous week before treatment. The items were summed for a total score that ranged from 0 to 64 (NCT01589302)
Timeframe: Up to 2 years

Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II)

The Beck Depression Inventory-2nd edition is a 21-item measure of depressive symptoms. Scores were calculated representing the cognitive-affective and the somatic symptoms associated with depression (e.g. sadness, pessimism, loss of pleasure) during past month on scale from 0 to 3. Items were summed, with higher scores indicating more depressive symptoms. The scores on the scale from range from 0 to 42. (NCT01589302)
Timeframe: at 5 months

Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention

The number of participants with successful Allogenic Stem Cell Transplant (NCT01589302)
Timeframe: Up to 2 years

Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory

The Fatigue Interference quality of life measures is a 11-item self reported questionnaire used to measure frequency, severity and daily pattern of fatigue Symptoms as well as impact of QOL in the past week. The Total Disruption Index (TDI) an 7 item subset of FSI was used. Items were rated on a 11-point Likert scale from 0=no interference to 10=extreme interference. Total scores could range from 0 to 70, with higher scores indicating greater fatigue interference. (NCT01589302)
Timeframe: at 5 months

Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study

SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning. (NCT01589302)
Timeframe: at 5 months

Negative Mood Quality of Life Measured by a 37-item Questionnaire

The Profile of Mood States-Short Form (POMS-SF) yields six subscales, Tension, Depression, Anger, Vigor, Fatigue, and Confusion. A total mood disturbance score is found by summing the six subscales. Total Mood Disturbance (TMD) scores range from -24 to 124 with higher scores indicating greater mood disturbance. (NCT01589302)
Timeframe: at 5 months

Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey

Physical Health Quality of life measures were administered during screening and on Days 1 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru Cycle 24 and at time of progression and /or end of treatment. SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning. (NCT01589302)
Timeframe: up to 5 months

Resistance Studies of Ibrutinib

Percentage of patients with BTK C481S mutation or PLCG2 mutation (NCT01589302)
Timeframe: Up to 4 years

Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale

Sleep problems quality of life measures is a six-item sleep problems index I of the Medical Outcomes Study-Sleep Scale used to assess sleep problems. Participants reported how often they experience six specific difficulties with sleep on a 6-point Likert scale (1=All of the time to 6=None of the time). Scores transformed into a 0-100 scale with higher scores indicating greater sleep problems. (NCT01589302)
Timeframe: at 5 months

2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765

Time from date of first treatment with ibrutinib until the date of progression or death from any cause. Those alive and progression free are censored at the date of last clinical assessment. (NCT01589302)
Timeframe: 2 years

Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines

Responders were subjects who achieved a complete response (CR), partial response (PR) or PR with persistent lymphocytosis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01589302)
Timeframe: up to 2 years

Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.

We will summarize our findings for this endpoint independently as well within each cohort (del17p vs other cytogenetic groups). We will evaluate the proportion of patients who are progression-free and alive at two years or have gone on to transplant (treatment successes) over the total number of evaluable patients; eligible patients who received at least one dose of therapy are considered evaluable. Assuming that the number of treatment successes as defined above is binomially distributed, we will also include 95% binomial confidence intervals for the estimates corresponding to each cohort. (NCT01589302)
Timeframe: up to 2 years

Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients

The 6 month overall response rates overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT01589302)
Timeframe: Up to 6 months

Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Adverse events grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with the attribution of either definite, possible or probable related. (NCT01589302)
Timeframe: Up to 2 years post treatment

Percentage of Patients With Overall Survival (OS)

Time from date of first treatment with ibrutinib until the date of death from any cause or the date of last contact for those alive. (NCT01589302)
Timeframe: 2 years

An Additional Endpoint Analysis Would Assess the MMT-8 Score in Patients With Muscle Disease as Measured at 3 and 6 Months Compared to Baseline.

"MMT-8 (Manual Muscle Testing-8) score is a validated tool to assess muscle strength. Calculate the mean change in MMT-8 score at 3 and 6 month(s) compared to baseline in patients with muscle disease.~Units: Units on a scale. Scale goes from 0-150. 150 is perfect strength." (NCT03529955)
Timeframe: Data collected at 3 and 6 months after baseline visit

An Additional Secondary Endpoint Analysis Would Assess Quality of Life as Measured at 3 Months Compared to Quality of Life Measured at 6 Months

"Dermatology Life Quality Index (DLQI) is a validated tool to measure quality of life in patients with skin disease. Complete response is defined by a DLQI of zero at 3, and 6 months. Partial response is defined by a decrease of DLQI of at least 5 points at 3, and 6 months compared to baseline. Calculation is performed as the DLQI at 3, and 6 months minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF).~Units : Units on a scale from 0-30, higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 3 and 6 months after baseline visit

An Additional Secondary Endpoint Analysis Would be Durability of Response Measured Participants CDASI Activity Score or Change in Their CDASI Activity Score at 6 Months Compared to 3 Months.

"The durability of response will be measured using the CDASI activity score at 6 months minus CDASI activity score at 3 months. Complete response durability is defined as zero or minus difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Partial response durability is defined as >4 points difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Missing data will be handled using the last observation carried forward approach (LOCF).~CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 6 months compared to data collected at 3 months

The Primary Endpoint Analysis Would be Overall Response Rate Measured by the Number of Participants Experiencing at Least 4 Points Decrease in CDASI Activity Score at 3 Months.

"Cutaneous dermatomyositis disease area and severity index (CDASI) activity score is a validated tool to measure skin disease activity in dermatomyositis. The overall response rate (ORR) includes partial and complete responses. Complete response is defined by a CDASI activity score of zero. Partial response is defined by a decrease of CDASI activity score of at least 4 points. Calculation is performed as the CDASI activity score at 3 month(s) minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF).~CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit

2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up.

"The proportion of participants experiencing adverse events and serious adverse events was measured over 7 months period (6 months during the study and 1 month follow up) using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.~Grade refers to severity of the AE. The CTCAE displays Grades 1 to 5 with unique clinical descriptions of severity for each AE:~Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental Activity of Daily Living (ADL) Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE All adverse events subjects experienced were grade 1 or 2 which is mild to moderate in severity." (NCT03529955)
Timeframe: 7 months

An Additional Endpoint is to Assess the Gene Expression Profiling and Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline.

Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in gene expression profiling and immunohistochemistry stain. Gene expression profiling will be analyzed using inferential statistics with a False Discovery Rate (FDR) of < 0.05. (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit

An Additional Endpoint is to Assess the Immunohistochemistry Analysis Change on Skin Biopsies at 3 Months Compared to Baseline.

Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in immunohistochemistry stain. (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit

Duration of Response (DOR)

DOR is defined as the number of days from the date of first response (complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial remission [nPR], or partial remission [PR]) to the earliest recurrence or progressive disease. DOR was analyzed by Kaplan-Meier (K-M) methodology. (NCT02141282)
Timeframe: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort

Overall Response Rate (ORR)

Overall response rate is defined as the percentage of participants with an overall response (per the investigator assessment) 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) criteria. (NCT02141282)
Timeframe: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort

Overall Survival (OS)

OS is defined as the number of days from the date of first dose to the date of death for all dosed participants. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology. (NCT02141282)
Timeframe: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort

Progression-free Survival (PFS)

PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology. (NCT02141282)
Timeframe: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort

Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)

TNNT is defined as the number of days from the date of the first dose of venetoclax to the date of first dose of any non-protocol anti-leukemia therapy (NPT) or death from any cause. For participants who did not take NPT, their data was censored at the last known date to be free of NPT. TTNT was analyzed by Kaplan-Meier methodology. (NCT02141282)
Timeframe: Collected every 3 months for a period of 5 years after the last participant had enrolled into the study

Time to Progression (TTP)

"TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (PD).~TTP was analyzed by Kaplan-Meier (K-M) methodology." (NCT02141282)
Timeframe: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort

Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status

The rate of MRD response is defined as the percentage of participants who had MRD negative status. (NCT02141282)
Timeframe: Assessed at Week 24, Day 1; after the first Complete Response, Complete Remission with Incomplete Marrow Recovery, or Partial Response; at 12-week interval visits until two consecutive negative MRD levels were reported

Participants With >/= 95 % Bruton's Tyrosine Kinase (BTK) Occupancy

BTK occupancy level measured by fluorescent affinity probe just before dosing and at 4 and 24 hours post-dosing on days 1, 8, and 28 (but before the first dose of the next cycle) of each cycle. (NCT02801578)
Timeframe: 3 cycles, up to 90 days

Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I

To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting >7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting > 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade >2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting. (NCT02268851)
Timeframe: Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I

Duration of Response (DoR): Study Cohort

DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and date of first documented evidence of progressive disease or death or date of censoring. iWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (>=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years 11 months

Duration of Stable Disease or Better: Study Cohort

Duration of stable disease or better was defined as duration from the start of the treatment until the criteria for progression were met. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years and 11 months

Overall Response Rate (ORR) as Assessed International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008: Disease Cohort

ORR is percentage of participants achieving a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR) or PR. IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/L, platelets >100*10^9/L, Hgb >11 g/dL and absolute lymphocyte count <4000/mcL; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- >=50% drop in lymphocyte count from baseline or <=4.0*10^9/L with following: >=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, >=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils >1.5*10^9/L, Platelets>100000/mcL and Hgb>11 g/dL or >=50% improvement over baseline in all. This outcome measure was planned to be analyzed for specified arm only. (NCT02329847)
Timeframe: Up to 6 years 11 months

Overall Response Rate (ORR) as Assessed Non-Hodgkin Lymphoma (NHL), Cheson 2014: Disease Cohort

ORR defined as percentage of participants achieving a CR, CRi, nPR or PR. As per Non-Hodgkin Lymphoma, Cheson 2014, CR is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is >= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) >= 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. This outcome measure was planned to be analyzed for specified arms only. (NCT02329847)
Timeframe: Up to 6 years 11 months

Overall Survival (OS): Study Cohort

OS was defined as duration from the date of first dose of study drug to the date of the participant's death. (NCT02329847)
Timeframe: Up to 6 years 11 months

Percentage of Participants With Lymphoma-related Symptoms: Study Cohort

Percentage of participants with lymphoma-related symptoms were reported. These symptoms included B-symptoms, recurrent fever, night sweats, weight loss, other disease-related symptoms, itching, fatigue, physical discomfort and any other. (NCT02329847)
Timeframe: Up to 6 years 11 months

Percentage of Participants With Treatment-emergent Adverse Event (TEAEs): Study Cohort

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs for the treatment phase included events with an onset date/time on or after the start of study intervention through end of study were considered as treatment-emergent. (NCT02329847)
Timeframe: Up to 6 years 10 months

Progression-free Survival (PFS): Study Cohort

PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. Participants who were progression-free and alive or had unknown status were censored at the last tumor assessment. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology. (NCT02329847)
Timeframe: Up to 6 years 11 months

Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab

Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project). (NCT03689894)
Timeframe: 6 weeks, 3 months, and 6 months after initiation of treatment

Number of Participants With a Response

Over all Response = complete remission (CR) + partial remission (PR). Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; positive or negative minimal residual disease (MRD); Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts (NCT01520519)
Timeframe: 7 months

Progression Free Survival (PFS)

Progression free survival defined as the time interval from treatment to progressive disease or death, whichever happens earlier. Participants in complete remission (CR), partial remission (PR) or stable disease (SD) are all counted as progression-free. Survival or times to progression functions estimated using the Kaplan-Meier method. (NCT01520519)
Timeframe: up to 50 months

Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score

Mean change from baseline to Cycle 5 in the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) Global Health Status Score according to EORTC QLQ-C30 Scoring Manual (3rd Edition, 2001). For global health status, positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. A change in 5 to 10 points in either direction represents a small change; 10 to 20 points represents a moderate change and greater than 20 points represents a large change. (NCT01236391)
Timeframe: From Baseline to Cycle 5 (Week 20)

Number of Participants With Treatment Emergent Adverse Events (AEs)

Number of participants who had experienced at least one treatment emergent AE (NCT01236391)
Timeframe: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure

PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765

Area under the plasma concentration-time curve using data collected at 0, 1, 2, 4, 6-8, and 24 hours post dose (AUC0-24h) (NCT01236391)
Timeframe: Performed During the First Month of Receiving PCI-32765

Percentage of Participants Achieving Response

The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a >/= 50% decrease in the sum of the product of diameters of the target lesions, and >/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions. (NCT01236391)
Timeframe: The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months

Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib

(NCT01292135)
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

Incidence of Prolonged Hematologic Toxicity Started in Cycle 1

(NCT01292135)
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0

(NCT01292135)
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

Overall Incidence of Serious Adverse Events (SAEs)

(NCT01292135)
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])

Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. Assessment of response to treatment will be done every 2 cycles for the first 6 months and then every 3 months thereafter until disease progression or prior to the administration of a new anticancer therapy and at follow-up visits. (NCT01292135)
Timeframe: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.

Progression Free Survival Rate at 12 Months

Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size. (NCT01292135)
Timeframe: From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest.

Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline

(NCT01292135)
Timeframe: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.

Number of Participants With Treatment Emergent Adverse Events (AEs)

Number of participants who had experienced at least one treatment emergent AE (NCT01217749)
Timeframe: From first dose of study treatment to within 30 days of last dose or until study closure

Percentage of Participants Achieving Response

The primary endpoint for the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR), CR with incomplete blood count recovery (Cri), or partial response (PR), according to the guidelines from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL1) published in 2008 for CLL participants and International Working Group for non-Hodgkin's lymphoma (IWG NHL) 2007 criteria for SLL participants, with the modification that treatment-related lymphocytosis will not be considered progressive disease, as evaluated by the investigators. Assessment of disease is based on radiological exams, physical exam, hematological evaluations and, when appropriate, bone marrow results. (NCT01217749)
Timeframe: The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months

Progression Free Survival (PFS) at 12 Months

"Progressive disease for CLL (Hallek) is characterized by ≥1 of the following:~Appearance of any new lesion, eg lymph nodes (> 1.5 cm), de novo hepatomegaly or splenomegaly, or other organ infiltrates~Increase of ≥50%~in longest diameter of any previous site~in hepatomegaly or splenomegaly~in blood lymphocytes with ≥5x109/L B cells with enlarging lymph node, liver, or spleen~Progressive disease for B cell lymphoma (Cheson) is characterized by any new lesion or increase by ≥ 50% of previously involved sites from nadir:~Appearance of a new lesion(s) >1.5 cm in any axis, ≥ 50% increase in the SPD of >1 node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis~Lesions PET+ if FDG-avid lymphoma or PET+ before therapy~50% increase from nadir in the SPD of any liver or spleen lesions~New or recurrent BM involvement~Increase of ≥50% in blood lymphocytes with ≥5x109/L B cells within enlarging lymph node, liver, or spleen" (NCT01217749)
Timeframe: From first dose of study treatment until disease progression, death, or until 12 months

Safety During Dose-Limiting Toxicity (DLT) Observation Period

Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2 (NCT01217749)
Timeframe: 56 days for Group 1 and 28 days for Group 2

Number of Participants With Treatment Emergent Adverse Events (AEs)

Number of participants who had experienced at least one treatment emergent AE (NCT01744691)
Timeframe: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure

Overall Response Rate

The primary objective of this study is to evaluate the efficacy of ibrutinib in terms of ORR according to an Independent Review Committee (IRC). ORR based upon IRC assessment is the proportion of responders in the all treated population. Responders were subjects who achieved partial response (PR) or better, ie, complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR, per IWCLL 2008 criteria with the clarification for treatment-related lymphocytosis. (NCT01744691)
Timeframe: The median time on study for all treated participants is 33.3 (range 0.5 - 40.1) months

Change in Leukemia Cell Death

Stable isotopic labeling with deuterated water (2^H2O) to measure directly the effects of PCI-32765 (ibrutinib) on leukemia cell death in the peripheral blood of participants . (NCT01752426)
Timeframe: every three months, up to one year

Percentage of Recently Born Leukemia Cells Mobilized Into the Blood by PCI-32765 Treatment

Measurement of the fraction of recently born versus older leukemia cells in the peripheral blood of participants before and during PCI-32765 therapy, to determine the effects of PCI-32765 (ibrutinib) therapy on the birth rates of the leukemia cells. (NCT01752426)
Timeframe: every three months, up to one year

Intervention	Proportion of participants (Number)
Arm A (Ibrutinib, Rituximab)	0.988
Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	0.915

Intervention	Proportion of participants (Number)
Arm A (Ibrutinib, Rituximab)	0.894
Arm B (Rituximab, Fludarabine Phosphate, Cyclophosphamide)	0.729

Intervention	percentage of participants (Number)
Elderly Cohort	93.9
TP53 Cohort	95.8

Intervention	months (Median)
Ofatumumab (Arm A)	65.1
Ibrutinib (Arm B)	67.7

Intervention	percentage of participants (Number)
Ofatumumab (Arm A)	22.4
Ibrutinib (Arm B)	87.7

Intervention	percentage of participants (Number)
	IRR (Preferred Term)	By Customized SMQ
CLB+OB	8.6	9.5
IBR+OB	2.7	4.4

Intervention	percentage of participants (Number)
	Hgb Improvement in patient with baseline anemia	Platelet improvement in baseline thrombocytopenia
Ibrutinib (Arm B)	69.7	78.4
Ofatumumab (Arm A)	32.6	9.4

Intervention	Units on the scale (Mean)
	Lost weight	Dry mouth	Bruises	Abdominal discomfort	Temperature going up and down	Night sweats	Skin problems	Feel ill	Feel lethargic	Felt slowed down	Limited in planning activities	Worried about health in the future	Trouble with chest infections	Trouble with other infections	Repeated courses of antibiotics	Worried about picking up infection
Ibrutinib+BR	0.1	0.3	0.1	0.1	0.1	-0.6	0.4	0.1	0.1	0.3	0.2	0.0	0.2	0.7	0.9	0.3
Placebo+BR	0.0	0.1	0.0	0.0	0.0	-0.3	0.3	0.2	0.0	0.0	0.1	0.0	0.0	0.1	0.0	0.2

Intervention	months (Median)
Arm A (Rituximab, Bendamustine Hydrochloride)	50
Arm B (Ibrutinib)	NA
Arm C (Ibrutinib, Rituximab)	NA

Intervention	Participants (Count of Participants)
	Abnormal loss of weight	Blood pressure fluctuation	Blood pressure increased	Blood pressure decreased	Blood pressure systolic increased	Body temperature decreased	Body temperature increased	Bradycardia	Breath sounds abnormal	Cardiac murmur	Dyspnoea	Dyspnoea exertional	Heart rate increased	Heart rate irregular	Hypertension	Hypotension	Hyperpyrexia	Orthostatic hypotension	Palpitations	Pyrexia	Tachycardia	Weight decreased	Weight increased	White coat hypertension
Acalabrutinib	0	0	2	1	0	1	0	3	0	1	40	2	0	1	26	15	1	2	12	66	7	29	13	0
Ibrutinib	1	1	3	0	1	0	1	1	1	2	27	5	1	0	70	7	0	1	15	55	7	23	10	1

Intervention	Participants (Count of Participants)
	Abnormal, not clinically significant	Abnormal, clinically significant
Acalabrutinib	86	4
Ibrutinib	98	1

Intervention	Participants (Count of Participants)
	Baseline=0; Postbaseline=3	Baseline=1; Postbaseline=3	Baseline=2; Postbaseline=3	Baseline=0; Postbaseline=4	Baseline=1; Postbaseline=4	Baseline=2; Postbaseline=4
Acalabrutinib	0	3	4	0	0	0
Ibrutinib	1	5	1	0	0	0

Intervention	Participants (Count of Participants)
	Absolute neutrophil count (decreased)	Haemoglobin (decreased)	Platelets (decreased)	Leukocytes (decreased)	Leukocytes (increased)	Absolute lymphocyte count (ALC) (decreased)	ALC (increased)	Alanine aminotransferase (increased)	Albumin (decreased)	Alkaline phosphatase (increased)	Aspartate aminotransferase (increased)	Bilirubin (increased)	Calcium (decreased)	Calcium (increased)	Creatinine (increased)	Glucose (decreased)	Glucose (increased)	Phosphate (decreased)	Potassium (decreased)	Potassium (increased)	Sodium (decreased)	Sodium (increased)	Urate (increased)
Acalabrutinib	124	139	119	60	68	66	71	73	31	66	42	46	56	15	164	5	21	93	27	62	26	70	70
Ibrutinib	135	131	116	64	84	65	72	70	44	60	58	69	71	11	168	13	23	74	40	52	37	46	96

Intervention	proportion of participants (Number)
Arm A (CLL)	0.0400
Arm B (NHL)	0
Arm C (CLL With Richters)	0
Arm A (Continuation Phase)	0.4000
Arm C (Continuation Phase)	0

Intervention	proportion of participants (Number)
Arm A (Continuation Phase)	0.6000
Arm C (Continuation Phase)	0.1538

Authors	Studies
Abdel-Qadir, H	1
Sabrie, N	1
Leong, D	1
Pang, A	1
Austin, PC	1
Prica, A	2
Nanthakumar, K	1
Calvillo-Argüelles, O	1
Lee, DS	1
Thavendiranathan, P	1
Abrisqueta, P	2
Loscertales, J	7
Terol, MJ	3
Ramírez Payer, Á	2
Ortiz, M	1
Pérez, I	1
Cuellar-García, C	2
Fernández de la Mata, M	1
Rodríguez, A	1
Lario, A	1
Delgado, J	8
Godoy, A	1
Arguiñano Pérez, JM	1
Berruezo, MJ	1
Oliveira, A	1
Hernández-Rivas, JÁ	3
García Malo, MD	1
Medina, Á	1
García Martin, P	1
Osorio, S	1
Baltasar, P	1
Fernández-Zarzoso, M	1
Marco, F	1
Vidal Manceñido, MJ	1
Smucler Simonovich, A	1
López Rubio, M	1
Jarque, I	2
Suarez, A	1
Fernández Álvarez, R	1
Lancharro Anchel, A	1

Intervention	Months (Median)
Arm A (CLL)	10.6
Arm B (NHL)	48.6
Arm C (CLL With Richters)	11.5
Arm A (Continuation Phase)	11.7
Arm C (Continuation Phase)	13.3

Intervention	Months (Median)
Cohort 1	33.3
Cohort 2a	26.7
Cohort 2b	77.3
Cohort 2c	43.0
Cohort 3	NA
Cohort 4a	64.1
Cohort 4b	NA
Cohort 7	NA
Cohort 11	NA

Intervention	Months (Median)
Cohort 1	38.3
Cohort 2a	33.1
Cohort 2b	79.1
Cohort 2c	46.6
Cohort 3	NA
Cohort 4a	67.8
Cohort 4b	NA
Cohort 7	NA
Cohort 11	NA

Intervention	L/hr (Mean)
	Day 1	Day 8
Cohort 1	114	176
Cohort 10	156	167
Cohort 11	137	188
Cohort 2a	193	216
Cohort 2b	212	162
Cohort 2c	112	122
Cohort 3	265	131
Cohort 4a	169	344
Cohort 4b	108	191
Cohort 7	315	389
Cohort 8a	352	94.5
Cohort 8b	311	336
Cohort 9	142	132

Intervention	Participants (Count of Participants)
	Hemoglobin, platelets or neutrophils decreased	Absolute neutrophil count (decreased)	Hemoglobin (decreased)	Platelets (decreased)	Leukocytes (decreased)	Leukocytes (increased)	Absolute lymphocyte count (decreased)	Absolute lymphocyte count (increased)	Urate (increased)	Sodium (decreased)	Phosphate (decreased)	Potassium (increased)	Glucose (increased)	Alanine aminotransferase (increased)	Calcium (increased)	Aspartate aminotransferase (increased)	Magnesium (increased)	Potassium (decreased)	Albumin (decreased)	Calcium (decreased)	Alkaline phosphatase (increased)	Amylase (increased)	Bilirubin (increased)	Creatinine (increased)	Lipase (increased)
Ibrutinib Relapsed/Refractory Cohort	4	3	3	1	0	2	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ibrutinib-intolerant Cohort	14	11	3	4	3	7	2	7	8	2	1	1	3	1	0	0	0	0	0	0	0	0	0	0	0
Relapsed/Refractory Cohort	72	57	17	20	12	29	20	29	24	12	9	3	3	3	5	2	2	2	2	2	1	2	2	2	1
Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort	19	13	8	5	6	0	6	3	5	3	1	0	0	1	1	0	0	1	0	1	1	0	0	0	0
Treatment-naive Cohort	30	23	5	3	2	21	7	8	15	5	1	5	1	1	0	2	2	1	1	0	0	0	0	0	1

Intervention	Participants (Count of Participants)
	Any TEAEs	Any TESAEs
Ibrutinib Relapsed/Refractory Cohort	6	3
Ibrutinib-intolerant Cohort	33	20
Relapsed/Refractory Cohort	134	86
Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort	28	18
Treatment-naive Cohort	99	50

Intervention	Participants (Count of Participants)
	Atrial fibrillation	Ventricular tachyarrhythmias	Anemia	Neutropenia	Other Leukopenia	Thrombocytopenia	Major hemorrhage	Hepatotoxicity	Hypertension	Infections	Interstitial lung disease/Pneumonitis	Second primary malignancies, excluding non-melanoma skin	Tumor lysis syndrome
Ibrutinib Relapsed/Refractory Cohort	0	0	1	1	0	0	1	0	0	4	0	0	0
Ibrutinib-intolerant Cohort	4	0	4	5	1	4	4	1	7	25	0	3	0
Relapsed/Refractory Cohort	12	2	22	26	2	10	11	4	31	118	1	23	1
Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort	3	0	10	13	0	4	0	3	2	18	0	1	0
Treatment-naive Cohort	6	0	10	9	1	1	8	4	29	86	3	14	0

Intervention	patients (Number)
	Anemia	Febrible Neutropenia	Leukocytosis	Atrial Fibrillation	Diarrhea	Gastric Hemorrhage	Gastrointestinal Disorders-other	Mucositis Oral	Nausea	Death	Edema Limb	Fatigue	General Disorders and Admin Site Conditions	Cholecystitis	Bronchial Infection	Infections and Infestations-other	Lung Infection	Otitis Media	Sepsis	Skin Infection	Urinary Tract Infection	Alanine Aminotransferase Increased	Blood Bilirubin Increased	Lymphocyte Count Decreased	Lymphocyte Count Increased	Neutrophil Count Decreased	Platelet Count Decreased	White Blood Cell Decreased	Hyperuricemia	Hypophosphatemia	Arthralgia	Arthritis	Hematuria	Hypoxia	Respiratory Failure	Rash Maculo-papular	Hematoma	Hypertension
Treatment (Ibrutinib)	13	2	18	1	2	1	1	1	2	1	1	1	2	1	1	4	10	1	2	2	1	1	1	14	54	40	8	10	4	1	2	1	2	1	1	1	1	7

Intervention	Participants (Count of Participants)
	Headache Grade 1-2	Nausea Grade 1-2	Diarrhea Grade 1-2	Herpes Zoster Grade 1-2	Influenza Grade 1-2	Pneumonia Grade 1-2	Acute sinusitis Grade 1-2	Hypertension Grade 1-2	Ocular pressure Grade 1-2
Dermatomyositis Patients With Refractory Cutaneous Disease	7	5	4	2	1	1	1	1	1

Intervention	Change (Number)
	Down regulated genes	Up regulated genes
Skin Biopsy at 3 Months Into Apremilast Therapy for Gene Expression Profiling	123	72
Skin Biopsy at Baseline for Gene Expression Profiling	0	0

Intervention	Percentage of positive cell detection (Mean)
	STAT1	STAT3
Skin Biopsy at 3 Months Into Apremilast Therapy for IHC	50.1	17.4
Skin Biopsy at Baseline for IHC	96.2	44.3

Intervention	months (Median)
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	35.1
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	55.4

Intervention	percentage of participants (Number)
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	64.8
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	69.4

Intervention	months (Median)
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	69.6
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	NA

Intervention	months (Median)
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	24.7
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	43.4

Intervention	months (Median)
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	36.1
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	43.4

Intervention	percentage of participants (Number)
	Peripheral blood	Bone marrow
ABT-199 After Ibrutinib Therapy: Main and Expansion Cohorts	30.8	6.6
ABT-199 After Idelalisib Therapy: Main and Expansion Cohorts	25.0	11.1

Intervention	Participants (Count of Participants)
CLL: Phase I Cohort 1	0
MCL: Phase 1 Cohort 1	0
CLL: Phase I Cohort 2	0
MCL: Phase I Cohort 2	0
CLL Phase I/IICohort 3 (RPD2)	0
MCL Phase I/II Cohort 3 (RPD2)	0

Intervention	Months (Median)
Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg	11.5
Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg	NA
Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg	19.2
Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg	10.2
Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg	NA
Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg	6.9

Intervention	Percentage of Participants (Number)
Ibrutinib and Nivolumab: Small Lymphocytic Lymphoma (SLL)	50.0
Ibrutinib and Nivolumab: Follicular Lymphoma (FL)	32.5
Ibrutinib and Nivolumab: Diffuse Large B-cell Lymphoma (DLBCL)	37.8
Ibrutinib and Nivolumab: Richter	65.0