adenine and Lymphoma, Mantle-Cell studies

Lymphoma, Mantle-Cell: A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).

Research Excerpts

Excerpt	Relevance	Reference
" Two weeks after the regular dose was restarted (month 3), the patient had repeated bleeding (patient was receiving aspirin for previous MI) and had to stop ibrutinib again."	4.93	Walking a tightrope: clinical use of ibrutinib in mantle cell lymphoma in the elderly. ( Ruella, M; Soubeyran, P, 2016)
" 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)
" The clinical behavior of MCL may be due to the complex pathophysiology of the disease which includes its genetic hallmark, the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1, alteration in the DNA damage response, and constitutive activation of key anti-apoptotic pathways such as phosphatidyl-inositol 3-kinase (PI3K)/Akt and nuclear factor-kB (NF-kB)."	3.78	Novel targeted therapies for mantle cell lymphoma. ( Alinari, L; Baiocchi, RA; Christian, B, 2012)
" The most common grade 3 adverse events were rash/pruritis/dermatitis (19%), diarrhea (11%), hyperglycemia (11%), and hypertension (11%)."	3.11	Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring. ( Batlevi, CL; De Frank, S; Drullinsky, P; Gerecitano, JF; Hamilton, A; Hamlin, PA; Horwitz, SM; Kumar, A; Matasar, MJ; Michaud, L; Moskowitz, A; Moskowitz, CH; Nakajima, R; Nichols, C; Rademaker, J; Salles, G; Schöder, H; Seshan, V; Stewart, CM; Straus, D; Tsui, DWY; Whiting, K; Younes, A; Zelenetz, AD, 2022)
" We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual reassessment method of 6 combinations of IBR (280 mg, 420 mg, and 560 mg by mouth daily) and VEN (max dose of 200 mg and 400 mg by mouth daily)."	3.11	Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. ( Budde, LE; Chen, RW; Cohen, JB; Kahl, BS; Petroni, GR; Portell, CA; Varhegyi, NE; Wages, NA; Williams, ME, 2022)
" We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients."	3.11	Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. ( Aymerich, M; Beà, S; Campo, E; Casanova, M; Cortés-Romera, M; de la Cruz, F; de la Fuente, A; García Sanz, R; Giné, E; González Barca, E; González-López, TJ; Jiménez Ubieto, A; López Jimenez, J; López-Guillermo, A; Marín-Niebla, A; Martín García-Sancho, A; Medina Herrera, A; Muntañola, A; Nadeu, F; Rodríguez, S; Rotger, A; Setoain, X; Terol, MJ, 2022)
" 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)
"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)
"Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting."	2.84	Activity of lenalidomide in mantle cell lymphoma can be explained by NK cell-mediated cytotoxicity. ( Apollonio, B; Chiu, H; Chopra, R; Couto, S; Flynt, E; Gandhi, AK; Hagner, PR; Ortiz, M; Ramsay, AG; Thakurta, A; Trotter, M; Waldman, MF; Wang, M, 2017)
"Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma."	2.82	Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. ( Addison, A; Badillo, M; Champlin, R; Chen, W; Chuang, H; DeLa Rosa, M; Fayad, L; Hagemeister, F; Lam, L; Lee, H; Li, S; Medeiros, LJ; Nomie, K; Oki, Y; Romaguera, J; Samaniego, F; Santos, D; Turturro, F; Wagner-Bartak, N; Wang, ML; Westin, J; Young, KH; Zhang, H; Zhang, L; Zhao, D, 2016)
" A total of 8/16 patients (50%) had at least one grade 3 adverse event (AE), and 5 (31."	2.82	Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma. ( Choi, I; Fukuhara, N; Hatake, K; Ishikawa, T; Kinoshita, T; Kitano, T; Maruyama, D; Matsuno, Y; Nagai, H; Nishikawa, T; Nishikori, M; Shibayama, H; Takahara, S; Tobinai, K; Uchida, T, 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)
" Outcomes assessed included overall response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), and adverse events."	2.61	Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. ( Abhyankar, S; Kabadi, SM; Signorovitch, J; Song, J; Telford, C; Yao, Z; Zhao, J, 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)
"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)
" 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)
"Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL)."	1.62	Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study. ( Byfield, SD; Kabadi, SM; LE, L; Olufade, T, 2021)
"Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse."	1.62	Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients. ( Arasaretnam, A; Bishton, M; Bolam, S; Creasey, T; Crosbie, N; Dawi, S; Dutton, D; Eyre, TA; Follows, G; Goradia, H; Harrison, S; Johnston, R; Kirkwood, AA; Lambert, J; Lewis, D; McCulloch, R; McKay, P; McMillan, A; Miles, O; Osborne, W; Patmore, R; Phillips, N; Robinson, A; Rule, S; Wilson, MR, 2021)
"In severe enterovirus infections, we recommend subtyping for the development of efficient preventive and therapeutic strategies."	1.56	Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report. ( Cana, D; Hess, G; Higer, M; Podlech, J; Schadmand-Fischer, S; Schwarting, A; Teschner, D; Theobald, M; Wölfel, T, 2020)
"There are limited data on treatment patterns, adverse events (AEs), and economic burden in younger, commercially insured patients treated for mantle cell lymphoma (MCL)."	1.51	Treatment patterns, adverse events, healthcare resource use and costs among commercially insured patients with mantle cell lymphoma in the United States. ( Burudpakdee, C; Kabadi, SM; Near, A; Wada, K, 2019)
"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)
" The additive and synergistic inhibition of this combination additionally supports a therapeutic strategy involving lower dosing of each drug to reduce potential side effects."	1.48	Additive and synergistic inhibition of mantle cell lymphoma cell growth by combining olaparib with ibrutinib. ( Curtis, A; Rajan, S; Rueter, J; Shopland, L; Zhang, R, 2018)
"Lenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy."	1.46	Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004). ( Barnett, E; Bravo, MC; Ghosh, N; Goy, A; Hamadani, M; Lossos, IS; Martin, P; Phillips, T; Reeder, CB; Rule, S; Schuster, SJ; Wang, M, 2017)
"Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug."	1.43	Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report. ( Bilbault, P; Gourieux, B; Lambert Kuhn, E; Levêque, D; Lioure, B, 2016)
"Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively."	1.42	Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes. ( Champlin, RE; Cheah, CY; Chihara, D; Fowler, NH; Hagemeister, FB; Romaguera, JE; Seymour, JF; Wang, ML, 2015)
" We investigated the efficacy of the histone deacetylase (HDAC) inhibitor vorinostat combined with one of several B-cell receptor (BCR) signaling inhibitors on MCL cell death and the underlying mechanisms, using MCL cell lines."	1.42	The synergistic effect of BCR signaling inhibitors combined with an HDAC inhibitor on cell death in a mantle cell lymphoma cell line. ( Hagiwara, K; Iida, H; Kunishima, S; Miyata, Y; Nagai, H; Naoe, T, 2015)
" We here compare bortezomib with carfilzomib and LU-102 in MM and MCL in vitro with regard to their effects on pIκB/NF-κB signaling and their cytotoxic activity in combination with ibrutinib."	1.42	The novel β2-selective proteasome inhibitor LU-102 decreases phosphorylation of I kappa B and induces highly synergistic cytotoxicity in combination with ibrutinib in multiple myeloma cells. ( Bader, J; Besse, L; de Bruin, G; Driessen, C; Geurink, PP; Kisselev, AF; Kraus, J; Kraus, M; Liu, N; Overkleeft, H, 2015)

Research

Studies (208)

Authors

Clinical Trials (31)

Trial Overview

Trial Outcomes

Area Under the Concentration Curve of Ibrutinib During 24 Hours After Dosing at Steady State

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	152 (73.08)	24.3611
2020's	56 (26.92)	2.80

Authors	Studies
Yuan, J	1
Zhang, Q	9
Wu, S	2
Yan, S	1
Zhao, R	2
Sun, Y	7
Tian, X	2
Zhou, K	1
Stewart, CM	1
Michaud, L	1
Whiting, K	2
Nakajima, R	1
Nichols, C	2
De Frank, S	1
Hamlin, PA	2
Matasar, MJ	1
Gerecitano, JF	1
Drullinsky, P	1
Hamilton, A	1
Straus, D	1
Horwitz, SM	1
Kumar, A	2
Moskowitz, CH	1
Moskowitz, A	1
Zelenetz, AD	2
Rademaker, J	1
Salles, G	2
Seshan, V	2
Schöder, H	1
Younes, A	2
Tsui, DWY	1
Batlevi, CL	1
Portell, CA	3
Wages, NA	2
Kahl, BS	3
Budde, LE	1
Chen, RW	2
Cohen, JB	2
Varhegyi, NE	1
Petroni, GR	2
Williams, ME	4
Wang, M	20
Ramchandren, R	1
Chen, R	1
Karlin, L	1
Chong, G	1
Jurczak, W	11
Wu, KL	1
Bishton, M	2
Collins, GP	1
Eliadis, P	1
Peyrade, F	1
Lee, Y	1
Eckert, K	1
Neuenburg, JK	1
Tam, CS	8
Jain, P	4
Zhao, S	3
Lee, HJ	7
Hill, HA	2
Ok, CY	4
Kanagal-Shamanna, R	4
Hagemeister, FB	4
Fowler, N	4
Fayad, L	5
Yao, Y	7
Liu, Y	13
Moghrabi, OB	1
Navsaria, L	2
Feng, L	2
Nogueras Gonzalez, GM	2
Xu, G	3
Thirumurthi, S	3
Santos, D	4
Iliescu, C	1
Tang, G	2
Medeiros, LJ	4
Vega, F	2
Avellaneda, M	1
Badillo, M	9
Flowers, CR	2
Wang, L	8
Wang, ML	14
Giné, E	2
de la Cruz, F	1
Jiménez Ubieto, A	1
López Jimenez, J	1
Martín García-Sancho, A	2
Terol, MJ	1
González Barca, E	1
Casanova, M	1
de la Fuente, A	1
Marín-Niebla, A	2
Muntañola, A	1
González-López, TJ	1
Aymerich, M	1
Setoain, X	1
Cortés-Romera, M	1
Rotger, A	1
Rodríguez, S	1
Medina Herrera, A	1
García Sanz, R	1
Nadeu, F	2
Beà, S	2
Campo, E	2
López-Guillermo, A	2
Nastoupil, L	2
Westin, JR	1
Samaniego, F	3
Steiner, R	1
Nair, R	1
Iyer, SP	1
Xuelin, H	1
Wagner-Bartak, N	2
Lin, P	1
Wang, SA	1
Jorgensen, J	1
Yin, CC	1
Li, S	6
Patel, KP	1
Mu, J	2
Liu, M	4
Wang, J	11
Meng, J	1
Zhang, R	2
Jiang, Y	2
Deng, Q	2
Qualls, D	1
Lam, HY	1
Matasar, M	1
Owens, C	1
Espeleta, JA	1
Qiu, A	1
Subzwari, S	1
Biggar, E	1
Batlevi, C	1
Siddiqi, T	1
Coutre, S	2
McKinney, M	1
Barr, PM	3
Rogers, K	1
Mokatrin, A	1
Valentino, R	2
Szoke, A	1
Deshpande, S	4
Zhu, A	1
Arango-Hisijara, I	1
Osei-Bonsu, K	1
O'Brien, S	3
Zinzani, PL	2
Martelli, M	1
Ferrero, S	2
Gentile, M	2
Laurenti, L	1
Romana Mauro, F	1
Sportoletti, P	1
Tedeschi, A	2
Varettoni, M	1
Visco, C	1
Ye, H	2
Huang, S	6
Chen, Z	6
Jiang, VC	1
Sancho, JM	1
Fernández, S	1
Capote, FJ	1
Cañigral, C	1
Grande, C	1
Donato, E	1
Zeberio, I	1
Puerta, JM	1
Rivas, A	1
Pérez-Ceballos, E	1
Vale, A	1
Salar, A	1
González-Barca, E	1
Teruel, A	1
Pastoriza, C	1
Conde-Royo, D	1
Sánchez-García, J	1
Barrenetxea, C	1
Arranz, R	1
Hernández-Rivas, JÁ	3
Ramírez, MJ	1
Jiménez, A	2
Rubio-Azpeitia, E	1
Jerkeman, M	7
Trotman, J	1
Belada, D	1
Boccomini, C	1
Flinn, IW	1
Giri, P	1
Goy, A	6
Hermine, O	1
Hong, X	1
Kim, SJ	3
Lewis, D	2
Mishima, Y	1
Özcan, M	1
Perini, GF	1
Pocock, C	1
Song, Y	3
Spurgeon, SE	2
Storring, JM	1
Walewski, J	1
Zhu, J	4
Qin, R	1
Henninger, T	2
Howes, A	2
Le Gouill, S	5
Dreyling, M	12
Killock, D	2
Freeman, CL	1
Pararajalingam, P	1
Jin, L	1
Balasubramanian, S	2
Jiang, A	1
Xu, W	3
Grau, M	1
Zapukhlyak, M	1
Boyle, M	1
Hodkinson, B	1
Schaffer, M	1
Enny, C	3
Sun, S	3
Vermeulen, J	6
Morin, RD	2
Scott, DW	1
Lenz, G	3
Rai, S	1
Tanizawa, Y	1
Cai, Z	1
Huang, YJ	1
Taipale, K	1
Tajimi, M	1
Cliff, ERS	1
Dickinson, M	1
Ferhanoglu, B	1
Birtas Atesoglu, E	1
Ozbalak, M	1
Eşkazan, AE	1
Vorobyev, VI	2
Gemdzhian, EG	1
Fedorova, LV	1
Mikhailova, NB	1
Ilyasov, RK	1
Kaleikina, LP	1
Trubyakova, OS	1
Kaplanov, KD	1
Melnichenko, EV	1
Martynova, EV	1
Yakovleva, EP	1
Li, OY	1
Tarasenko, EV	1
Chumakova, EP	1
Bulieva, NB	1
Nesterova, ES	1
Margolin, OV	1
Zherebtsova, VA	1
Butaev, LS	1
Ptushkin, VV	2
Araujo-Ayala, F	1
Dobaño-López, C	1
Valero, JG	1
Gava, F	1
Faria, C	1
Norlund, M	1
Morin, R	1
Bernes-Lasserre, P	1
Serrat, N	1
Playa-Albinyana, H	1
Giménez, R	1
Lagarde, JM	1
Colomer, D	1
Bezombes, C	1
Pérez-Galán, P	1
Nishiyama-Fujita, Y	1
Nakazato, T	1
Ito, C	1
Ogura, S	1
Mizuno, K	1
Kamiya, T	1
Aisa, Y	1
Mori, T	1
Wang, HY	4
Liu, X	7
Nunez-Cruz, S	3
Jillab, M	1
Melnikov, O	1
Nath, K	2
Glickson, J	1
Wasik, MA	4
Jeon, YW	1
Yoon, S	1
Min, GJ	1
Park, SS	1
Park, S	3
Yoon, JH	1
Lee, SE	1
Cho, BS	1
Eom, KS	1
Kim, YJ	1
Kim, HJ	2
Lee, S	1
Min, CK	1
Lee, JW	1
Cho, SG	4
Kabadi, SM	4
Near, A	1
Wada, K	1
Burudpakdee, C	1
Liang, SH	1
Chiu, CF	1
Bai, LY	1
Telford, C	1
Abhyankar, S	1
Song, J	2
Signorovitch, J	1
Zhao, J	1
Yao, Z	1
Nakamura, K	1
Saburi, M	1
Kondo, Y	1
Soga, Y	1
Itani, K	1
Kohno, K	1
Otsuka, M	1
Nakayama, T	1
Zhou, X	2
Steinhardt, MJ	1
Düll, J	1
Krummenast, F	1
Danhof, S	1
Meckel, K	1
Nickel, K	1
Grathwohl, D	1
Leicht, HB	1
Rosenwald, A	4
Einsele, H	1
Rasche, L	1
Kortüm, M	1
Schmelz, JL	1
Cramer, F	1
Romaguera, JE	4
Mosna, K	1
Ladicka, M	1
Drgona, L	1
Vranovska, M	1
Hojsikova, I	1
Tomasova, R	1
Danihel, L	1
Kyselovic, J	1
Babal, P	1
Hanna, KS	1
Campbell, M	1
Husak, A	1
Sturm, S	1
Halim, AA	1
Alsayed, B	1
Embarak, S	1
Yaseen, T	1
Dabbous, S	1
Fontaine, O	1
Dueluzeau, R	1
Raibaud, P	1
Chabanet, C	1
Popoff, MR	1
Badoual, J	1
Gabilan, JC	1
Andremont, A	1
Gómez, L	1
Andrés, S	1
Sánchez, J	1
Alonso, JM	1
Rey, J	1
López, F	1
Yan, Z	1
Zhou, L	1
Zhao, Y	3
Huang, L	2
Hu, K	1
Liu, H	4
Wang, H	3
Guo, Z	1
Huang, H	4
Yang, R	1
Owen, TW	1
Al-Kaysi, RO	1
Bardeen, CJ	1
Cheng, Q	1
Cheng, T	1
Wang, B	4
Wu, X	3
Ochiai, T	1
Ishiguro, H	2
Nakano, R	2
Kubota, Y	2
Hara, M	1
Sunada, K	1
Hashimoto, K	1
Kajioka, J	1
Fujishima, A	1
Jiao, J	4
Gai, QY	3
Wang, W	3
Zang, YP	2
Niu, LL	2
Fu, YJ	3
Wang, X	5
Yao, LP	1
Qin, QP	1
Wang, ZY	1
Liu, J	4
Aleksic Sabo, V	1
Knezevic, P	1
Borges-Argáez, R	1
Chan-Balan, R	1
Cetina-Montejo, L	1
Ayora-Talavera, G	1
Sansores-Peraza, P	1
Gómez-Carballo, J	1
Cáceres-Farfán, M	1
Jang, J	1
Akin, D	1
Bashir, R	1
Yu, Z	1
Jiang, H	4
He, C	2
Xiao, Z	1
Xu, J	2
Sun, Q	1
Han, D	1
Lei, H	1
Zhao, K	2
Zhu, L	1
Li, X	5
Fu, H	2
Wilson, BK	1
Step, DL	1
Maxwell, CL	1
Gifford, CA	1
Richards, CJ	1
Krehbiel, CR	1
Warner, JM	1
Doerr, AJ	1
Erickson, GE	1
Guretzky, JA	1
Rasby, RJ	1
Watson, AK	1
Klopfenstein, TJ	1
Liu, Z	3
Pham, TD	1
Lee, BK	1
Yang, FC	1
Wu, KH	1
Lin, WP	1
Hu, MK	1
Lin, L	3
Shao, J	1
Sun, M	1
Zhang, X	6
Xu, N	1
Wang, R	1
Liu, S	1
He, H	1
Dong, X	2
Yang, M	2
Yang, Q	1
Duan, S	1
Yu, Y	2
Han, J	2
Zhang, C	3
Chen, L	4
Yang, X	1
Li, W	3
Wang, T	2
Campbell, DA	1
Gao, K	1
Zager, RA	1
Johnson, ACM	1
Guillem, A	1
Keyser, J	1
Singh, B	1
Steubl, D	1
Schneider, MP	1
Meiselbach, H	1
Nadal, J	1
Schmid, MC	1
Saritas, T	1
Krane, V	1
Sommerer, C	1
Baid-Agrawal, S	1
Voelkl, J	1
Kotsis, F	1
Köttgen, A	1
Eckardt, KU	1
Scherberich, JE	1
Li, H	4
Yao, L	2
Sun, L	3

Trial	Phase	Enrollment	Study Type	Start Date	Status
Phase Ib Clinical Trial of Buparlisib and Ibrutinib in Mantle Cell Lymphoma, Follicular Lymphoma and Diffuse Large B Cell Lymphoma[NCT02756247]	Phase 1	37 participants (Actual)	Interventional	2016-05-09	Completed
Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma[NCT02419560]	Phase 1	37 participants (Actual)	Interventional	2015-04-30	Completed
Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma[NCT03112174]	Phase 3	352 participants (Actual)	Interventional	2017-06-29	Active, not recruiting
A Phase II Study of Ibrutinib Plus Rituximab With Hyper-CVAD Consolidation in Newly Diagnosed Young Patients With Mantle Cell Lymphoma: A Window Period for Bioimmunotherapy Before Chemotherapy[NCT02427620]	Phase 2	131 participants (Anticipated)	Interventional	2015-06-03	Active, not recruiting
A Phase II Study of Ibrutinib Plus Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma or Elderly Patients With Newly Diagnosed MCL[NCT01880567]	Phase 2	113 participants (Actual)	Interventional	2013-07-15	Active, not recruiting
Multicentric Phase II Trial to Evaluate the Efficacy and Safety of Ibrutinib in Combination With Rituximab in Patients With Indolent Clinical Forms of Mantle Cell Lymphoma[NCT02682641]	Phase 2	50 participants (Anticipated)	Interventional	2016-05-18	Active, not recruiting
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma[NCT01776840]	Phase 3	523 participants (Actual)	Interventional	2013-05-16	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 2 Study of ABT-199 in Combination With Ibrutinib in the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma (AIM Study)[NCT02471391]	Phase 2	37 participants (Actual)	Interventional	2015-07-22	Active, not recruiting
A Phase I/II Trial of Obinutuzumab, ABT-199 (GDC-0199) Plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma Patients[NCT02558816]	Phase 1/Phase 2	48 participants (Actual)	Interventional	2015-10-14	Active, not recruiting
A Phase 2, Multicenter, Randomized Open-Label Study To Determine the Efficacy of Lenalidomide (Revlimid®) Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma[NCT00875667]	Phase 2	254 participants (Actual)	Interventional	2009-04-30	Completed
A Multicenter, Observational Study to Evaluate the Effectiveness of Lenalidomide (Revlimid®) in Subjects With Mantle Cell Lymphoma Who Have Relapsed or Progressed After Treatment With Ibrutinib or Are Refractory or Intolerant to Ibrutinib.[NCT02341781]		30 participants (Actual)	Observational	2015-04-30	Completed
A Phase II Trial of Ibrutinib, Lenalidomide and Rituximab for Patients With Relapsed/Refractory Mantle Cell Lymphoma[NCT02460276]	Phase 2	50 participants (Actual)	Interventional	2015-04-30	Completed
Long-term Effect of Chronic Ibrutinib Therapy on Left Atrial Function[NCT03751410]		40 participants (Actual)	Observational [Patient Registry]	2018-12-01	Completed
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 II Study of Palbociclib (PD-0332991) in Combination With Ibrutinib in Patients With Previously Treated Mantle Cell Lymphoma[NCT03478514]	Phase 2	39 participants (Actual)	Interventional	2018-09-11	Active, not recruiting
A Phase I Trial of Ibrutinib Plus PD 0332991 (Palbociclib) in Patients With Previously Treated Mantle Cell Lymphoma[NCT02159755]	Phase 1	28 participants (Actual)	Interventional	2014-05-20	Active, not recruiting
Phase Ib Dose Finding Study of ABT-199 (A-1195425.0) Plus Ibrutinib (PCI-32765) and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell NHL (DLBCL)[NCT03136497]	Phase 1	10 participants (Actual)	Interventional	2017-09-05	Active, not 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)
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 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
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
Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics[NCT00114738]	Phase 2	53 participants (Actual)	Interventional	2005-06-15	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
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
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
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 Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy[NCT01646021]	Phase 3	280 participants (Actual)	Interventional	2012-12-10	Completed
Bortezomib Combined With Fludarabine and Cytarabine for Mantle Cell Lymphoma Patients：a Single Arm, Open-labelled, Phase 2 Study[NCT03016988]	Phase 2	50 participants (Anticipated)	Interventional	2017-01-31	Not yet recruiting
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 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)[NCT02169180]	Phase 2	16 participants (Actual)	Interventional	2014-08-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Area under the concentration curve of ibrutinib during 24 hours after dosing at steady state was determined using PopPK modeling. (NCT01776840)
Timeframe: Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

Complete Response Rate

Intervention	nanogramhour per milliliter (ngh/mL) (Mean)
Ibrutinib + BR (Treatment B)	425

Complete response (CR) rate is defined as the percentage of participants who achieve CR (based on investigator assessment) on or prior to the initiation of subsequent anticancer therapy. Criteria for CR: disappearance of all evidence of disease; mass of any size permitted if positron emission tomography (PET) negative; regression to normal size on computed tomography (CT); spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. (NCT01776840)
Timeframe: Up to 97 months

Duration of Complete Response (DoCR)

Intervention	percentage of participants (Number)
Ibrutinib + BR (Treatment B)	65.5
Placebo + BR (Treatment A)	57.6

Duration of complete response (DoCR) was defined as the interval between the date of initial documentation of a CR and the date of first documented evidence of PD or death whichever occurs first, for participants who achieved CR. (NCT01776840)
Timeframe: Up to 97 months

Duration of Response (DoR)

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	NA
Placebo + BR (Treatment A)	78.1

Duration of Response (DoR) was defined as the interval between the date of initial documentation of a response including PR and the date of first documented evidence of PD or death. (NCT01776840)
Timeframe: Up to 97 months

Maximum Observed Plasma Concentration of Ibrutinib

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	81
Placebo + BR (Treatment A)	63.5

Maximum observed plasma concentration of ibrutinib was determined using PopPK modeling. (NCT01776840)
Timeframe: Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

Minimal Residual Disease (MRD)-Negative Response Rate

Intervention	ng/mL (Mean)
Ibrutinib + BR (Treatment B)	74.5

Minimal residual disease negative rate was defined as the percentage of participants with a best overall response of CR with MRD-negative disease status (that is, <5 mantle cell lymphoma [MCL] cell per 10,000 leukocytes for detection using the MRD assay), as assessed by flow cytometry of a bone marrow and/or peripheral blood sample. (NCT01776840)
Timeframe: Up to 97 months

Minimum Observed Plasma Concentration of Ibrutinib

Intervention	percentage of participants (Number)
Ibrutinib + BR (Treatment B)	62.1
Placebo + BR (Treatment A)	56.5

Minimum observed plasma concentration of ibrutinib was determined using PopPK modeling. (NCT01776840)
Timeframe: Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

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

Intervention	nanograms per milliliter (ng/mL) (Mean)
Ibrutinib + BR (Treatment B)	3.90

Number of participants with TEAEs were reported. Treatment-emergent adverse events are defined as adverse events with onset or worsening on or after date of first dose of study treatment up to and including 30 days after date of last dose of study medication, or the initiation of subsequent anticancer therapy, whichever is earlier. (NCT01776840)
Timeframe: Up to 97 months

Oral Plasma Clearance (CL/F) of Ibrutinib

Intervention	Participants (Count of Participants)
Ibrutinib + BR (Treatment B)	259
Placebo + BR (Treatment A)	257

CL/F of Ibrutinib was determined using population pharmacokinetics (PopPK modeling). (NCT01776840)
Timeframe: Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

Oral Volume of Distribution at Steady State of Ibrutinib

Intervention	liter per hour (L/h) (Mean)
Ibrutinib + BR (Treatment B)	1123

Oral volume of distribution at steady state of ibrutinib was determined using PopPK modeling. (NCT01776840)
Timeframe: Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

Overall Survival

Intervention	liter (Mean)
Ibrutinib + BR (Treatment B)	7286

Overall survival is defined as the time from the date of randomization to the date of the participant's death. (NCT01776840)
Timeframe: Up to 97 months

Percentage of Participants With Overall Response

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	NA
Placebo + BR (Treatment A)	NA

Percentage of participants with overall response that is participants who achieved CR or PR was reported. Criteria for CR: disappearance of all evidence of disease; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. Criteria for PR: greater than or equal to (>=) 50% decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. (NCT01776840)
Timeframe: Up to 97 months

Progression-free Survival (PFS)

Intervention	percentage of participants (Number)
Ibrutinib + BR (Treatment B)	89.7
Placebo + BR (Treatment A)	88.5

Progression-free survival (PFS) is defined as the interval between the date of randomization to the date of disease progression (PD) or relapse from complete response (CR) or death, whichever is first reported. Disease assessments were based on the 2007 Revised Response Criteria for Malignant Lymphoma. PD is defined as any new lesion or increase by 50 percent (%) of previously involved sites from nadir (PD criteria: Appearance of new nodal lesion 1.5 centimeters [cm] in any axis, 50% increase in sum of product of diameters [SPD] of greater than [>] 1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis). (NCT01776840)
Timeframe: Up to 97 months

Time to Response

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	80.6
Placebo + BR (Treatment A)	52.9

Time to response was defined as the interval between the date of randomization and the date of initial documentation of a response. (NCT01776840)
Timeframe: Up to 97 months

Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Questionnaire

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	2.79
Placebo + BR (Treatment A)	2.79

"Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening of participant symptoms. Worsening was defined by a 5-point decrease from baseline, death, or a missing assessment due to being too ill, whichever occurred first. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life." (NCT01776840)
Timeframe: Up to 97 months

Time-to-Next Treatment

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	17.4
Placebo + BR (Treatment A)	22.2

Time-to-next treatment was measured from the date of randomization to the start date of any anti-mantle cell lymphoma (anti-MCL) treatment subsequent to the study treatment. (NCT01776840)
Timeframe: Up to 97 months

Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review

Intervention	months (Median)
Ibrutinib + BR (Treatment B)	NA
Placebo + BR (Treatment A)	92.0

Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis

Intervention	Weeks (Median)
Lenalidomide	69.6
Investigators Choice	45.1

Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review

Intervention	Weeks (Median)
Lenalidomide	70.1
Investigators Choice	91.7

Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks

Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis

Intervention	weeks (Median)
Lenalidomide	121.0
Investigators Choice	91.7

Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to the study discontinuation date of 09 October 2018; overall median follow-up time was 285 weeks

Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review

Intervention	weeks (Median)
Lenalidomide	120.6
Investigators Choice	91.7

PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks

Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis

Intervention	weeks (Median)
Lenalidomide	37.6
Investigators Choice	22.7

Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks

Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review

Intervention	weeks (Median)
Lenalidomide	37.3
Investigators Choice	23.6

Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants. ). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From randomization of study drug to time of first documented PR or better response; up to data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis

Intervention	Weeks (Median)
Lenalidomide	18.7
Investigators Choice	NA

Time to first response was defined as the time from first dose of study drug to the date of the first response (having at least a PR). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the subject was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Kaplan Meier Estimate of Time to Progression According to the IRC Central Review

Intervention	Weeks (Median)
Lenalidomide	23.9
Investigators Choice	40.0

Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis

Intervention	Weeks (Median)
Lenalidomide	39.3
Investigators Choice	24.7

Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator

Intervention	Weeks (Median)
Lenalidomide	39.3
Investigators Choice	24.7

Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. (NCT00875667)
Timeframe: From the date of the first treatment to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis

Intervention	weeks (Median)
Lenalidomide	24.4
Investigators Choice	17.9

Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. (NCT00875667)
Timeframe: From date of first dose of treatment to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit

Intervention	weeks (Median)
Lenalidomide	24.4
Investigators Choice	17.9

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-4.8
Investigators Choice	-4.1

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	3.2
Investigators Choice	2.9

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-0.3
Investigators Choice	-3.5

"The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).~The EORTC QLQ-C30 Diarhoea Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement." (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014

Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Least Squares Mean)
Lenalidomide	-7.2
Investigators Choice	-5.8

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-7.3
Investigators Choice	-5.8

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	6.9
Investigators Choice	3.7

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-4.9
Investigators Choice	-2.9

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-10.9
Investigators Choice	-2.3

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Scale was scored between 0 and 100, with a higher score representing a higher quality of life. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	4.6
Investigators Choice	5.6

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-12.8
Investigators Choice	-7.6

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Scale was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-2.3
Investigators Choice	-0.6

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014

Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	-5.8
Investigators Choice	-3.5

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	3.4
Investigators Choice	-1.8

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit

Intervention	units on a scale (Mean)
Lenalidomide	3.1
Investigators Choice	5.0

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review

Intervention	units on a scale (Mean)
Lenalidomide	5.1
Investigators Choice	3.8

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response (CR), Complete Response unconfirmed (CRu) or Partial Response (PR). Participants who discontinued before any response had been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis

Intervention	Percentage of Participants (Number)
Lenalidomide	40.0
Investigators Choice	10.7

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review

Intervention	Percentage of Participants (Number)
Lenalidomide	45.9
Investigators Choice	22.6

Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis

Intervention	Percentage of Participants (Number)
Lenalidomide	69.4
Investigators Choice	63.1

Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. (NCT00875667)
Timeframe: From date of randomization to the discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Constipation

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain was scored between 0 and 100, with a higher score representing a higher quality of life. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.

Number of Participants With Treatment Emergent Adverse Events

Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild Adverse Event (AE), Grade 2 = Moderate AE, Grade 3 = Severe and Undesirable AE, Grade 4 = Life-threatening or Disabling AE, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A Treatment Emergent Adverse event (TEAE) is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. (NCT00875667)
Timeframe: From the date of the first dose of study drug to 28 days after the last dose, up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm

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

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

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

Count of Participants With Serious and Non-Serious Adverse Events

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT00114738)
Timeframe: Date treatment consent signed to date off study, approximately 143 months and 7 days

Median Overall Survival (OS)

Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test. (NCT00114738)
Timeframe: up to 9.9 years

Overall Progression Free Survival

Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes. (NCT00114738)
Timeframe: up to 9.9 years

Overall Survival

Progression Free Survival (PFS)

Clinical Response

Clinical response is assessed by the response criteria for lymphomas and is defined as a fraction of patients who have a complete response (CR) or a complete response (CR) + partial response (PR). A complete response is disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g. lactate dehydrogenase) definitely assignable to the lymphoma. Partial response is ≥50% decreased in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Progressive disease is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen, ≥50% increase in the absolute number of circulating lymphocytes. (NCT00114738)
Timeframe: up to 22 weeks after initiation of therapy

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

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. (NCT01105247)
Timeframe: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss)

The AUC-ss is the area under the plasma concentration time curve observed during steady state. (NCT01646021)
Timeframe: Cycle 1 and 2 (Day 1): Predose, 1, 2, 4 hr. postdose; Cycle 3 (day 1): Predose (Each cycle is of 21 days)

Duration of Response

Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. The analysis was based on the investigator assessment. (NCT01646021)
Timeframe: Approximately up to 48 months

Extent of Exposure of Time

Extent of exposure is defined as the duration of the treatment administered during the study. Duration of exposure is calculated as the number of months between the start and end of treatment. (NCT01646021)
Timeframe: Approximately up to 46.8 months

Number of Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)

Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study. (NCT01646021)
Timeframe: Approximately up to 28.2 months

Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI)

Number of Participants Affected With Treatment-emergent Adverse Events

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. (NCT01646021)
Timeframe: Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years)

Number of Participants With Biomarkers That Alter B-cell Receptor (BCR) Signaling or Activate Alternative Signaling Pathways and to Explore Their Association With Response or Resistance to Ibrutinib

Biomarker evaluations to identify markers altering BCR signaling or activate alternative signaling pathways and explore their association with response or resistance to ibrutinib. Next-generation sequencing at baseline identifies possible primary resistance mutations and those found only at progression are acquired mutations on therapy. (NCT01646021)
Timeframe: Approximately up to 28.2 months

One Year Survival Rate

One -year survival rate, defined as the proportion of participants who were alive 1 year after randomization. (NCT01646021)
Timeframe: Month 12

Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR. (NCT01646021)
Timeframe: Approximately up to 48 months

Overall Survival (OS)

Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause. (NCT01646021)
Timeframe: Approximately up to 48 months

Progression Free Survival (PFS)

PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to [>=] 50 percent [%] of previously involved sites from nadir). (NCT01646021)
Timeframe: Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)

Progression-Free Survival 2

Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy. (NCT01646021)
Timeframe: Approximately up to 48 months

Time to Response

Time to response for participants with CR/PR, defined as the interval between the date of randomization and date of initial documentation of response. (NCT01646021)
Timeframe: Approximately up to 2.8 years

Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)

Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life. (NCT01646021)
Timeframe: Approximately up to 48 months

Time-to-Next Treatment

Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment. (NCT01646021)
Timeframe: Approximately up to 48 months

Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)

The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment

The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and possible total score range -0.594 to 1; higher score indicates a better health state. (NCT01646021)
Timeframe: Baseline, Cycle 2, 3, 4, 5, 6, 7, 8, 11, 14, 17, 20, 28, 36 and End of treatment (approximately up to 23 months)

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

Intervention	units on a scale (Mean)
	Baseline	Change from Baseline to Cycle 3 Day 1	Change from Baseline to Cycle 5 Day 1	Change from Baseline to Cycle 7 Day 1	Change from Baseline to Cycle 9 Day 1	Change from Baseline to Treatment Discontinuation
Investigators Choice	16.2	-0.8	5.1	-12.5	-11.1	5.4
Lenalidomide	18.1	2.5	1.9	-2.3	-4.3	4.8

Intervention	units on a scale (Mean)
	Baseline	Change from Baseline to Cycle 3 Day 1	Change from Baseline to Cycle 5 Day 1	Change from Baseline to Cycle 7 Day 1	Change from Baseline to Cycle 9 Day 1	Change from Baseline to Treatment Discontinuation
Investigators Choice	83.6	-2.3	1.3	4.2	5.6	-2.3
Lenalidomide	84.6	0.0	-1.9	-3.2	-2.5	-5.1

Intervention	units on a scale (Mean)
	Baseline	Change from Baseline to Cycle 3 Day 1	Change from Baseline to Cycle 5 Day 1	Change from Baseline to Cycle 7 Day 1	Change from Baseline to Cycle 9 Day 1	Change from Baseline to Treatment Discontinuation
Investigators Choice	8.6	-0.8	1.3	0.0	0.0	0.8
Lenalidomide	12.5	6.3	4.2	3.5	-0.7	10.2

Intervention	units on a scale (Mean)
	Baseline	Change from Baseline to Cycle 3 Day 1	Change from Baseline to Cycle 5 Day 1	Change from Baseline to Cycle 7 Day 1	Change from Baseline to Cycle 9 Day 1	Change from Baseline to Treatment Discontinuation
Investigators Choice	12.6	-3.1	1.3	-4.2	0.0	0.0
Lenalidomide	15.7	-3.5	-4.2	2.4	-2.1	1.6

Intervention	units on a scale (Mean)
	Baseline	Change from Baseline to Cycle 3 Day 1	Change from Baseline to Cycle 5 Day 1	Change from Baseline to Cycle 7 Day 1	Change from Baseline to Cycle 9 Day 1	Change from Baseline to Treatment Discontinuation
Investigators Choice	21.2	-0.8	0.0	4.2	5.6	0.8
Lenalidomide	26.5	-1.6	-1.4	-2.9	1.4	6.0

Intervention	units on a scale (Mean)
	Baseline	Cycle 3 Day 1	Cycle 5 Day 1	Cycle 7 Day 1	Cycle 9 Day 1	Treatment Discontinuation
Investigators Choice	13.7	-1.2	-2.6	0.0	-2.8	3.5
Lenalidomide	22.6	-2.2	-0.2	3.2	-3.2	4.6

Intervention	Participants (Count of Participants)
	Any TEAE	Any TEAE Grade 3 AE	Any TEAE Grade 4 AE	Any TEAE Grade 5 AE	Any TEAE Related to the IP	Any Grade 3 AE Related to IP	Any Grade 4 AE Related to IP	Any Grade 5 AE Related to IP	Any Serious Adverse Event (SAE)	Any SAE Related to IP	Any TEAE Leading to Stopping of IP	Any Treatment Related AE Leading to Stopping IP	TEAE Leading to Dose Reduction/Interruption	Related AE Leading to Dose Reduct/Interruption	TEAE Leading to Dose Reduction	Related AE Leading to Dose Reduction	TEAE Leading to Dose Interruption	Related AE Leading to Dose Interruption
Investigators Choice	69	49	29	2	51	36	19	0	22	12	14	7	33	29	13	10	28	25
Lenalidomide	159	126	56	15	141	106	46	0	75	38	31	18	114	103	72	69	110	98

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	Percentage of patients (Number)
	Overall Response (CR+PR)	Complete Response	Stable Disease	Progressive Disease	Not Evaluable
EPOCH-R+Bortezomib	92.5	86.7	3.8	1.9	1.9

Intervention	Days (Mean)
	Mean days of hospitalization	Mean days of emergency room visits
Ibrutinib	19.7	1.8
Temsirolimus	20.3	1.6

Intervention	Units on scale (Mean)
	Baseline	Change at Cycle 2	Change at Cycle 3	Change at Cycle 4	Change at Cycle 5	Change at Cycle 6	Change at Cycle 7	Change at Cycle 8	Change at Cycle 11	Change at Cycle 14	Change at Cycle 17	Change at Cycle 20	Change at Cycle 28	Change at Cycle 36	Change at End of treatment
Ibrutinib	0.7	0.0	0.1	0.0	0.0	0.1	0.0	0.0	0.0	0.0	0.0	0.0	-0.1	0.0	0.0
Temsirolimus	0.7	0.0	-0.1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1	-0.1	-0.1

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

Article	Year
Use of BTK inhibitors with focus on ibrutinib in mantle cell lymphoma: An expert panel opinion statement. Hematological oncology, 2022, Volume: 40, Issue:4 Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Humans; Lymphoma, Mantle	2022
Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Clinical therapeutics, 2019, Volume: 41, Issue:11 Topics: Adenine; Antineoplastic Agents; Benzamides; Bortezomib; Humans; Lenalidomide; Lymphoma, Mantle-Cell;	2019
The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2020, Volume: 26, Issue:5 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Benzamides; Humans; Immunothera	2020
The Egyptian journal of chest diseases and tuberculosis, 2016, Volume: 65, Issue:1 Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor P	2016
Incorporating acalabrutinib, a selective next-generation Bruton tyrosine kinase inhibitor, into clinical practice for the treatment of haematological malignancies. British journal of haematology, 2021, Volume: 193, Issue:1 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Benzamides; Clinical Trials a	2021
Current Status of Bruton's Tyrosine Kinase Inhibitor Development and Use in B-Cell Malignancies. Drugs & aging, 2017, Volume: 34, Issue:7 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Atrial Fibrillation; Drug Discovery; Graft vs Host Dis	2017
Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2018, Volume: 24, Issue:7 Topics: Adenine; Aged; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Male; Piperidi	2018
Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies. British journal of haematology, 2017, Volume: 179, Issue:3 Topics: Adenine; Antineoplastic Agents; Humans; Lymphoma, Mantle-Cell; Piperidines; Pyrazoles; Pyrimidines;	2017
Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects. British journal of haematology, 2018, Volume: 181, Issue:3 Topics: Adenine; Drug Resistance, Neoplasm; Humans; Lymphoma, Mantle-Cell; Piperidines; Pyrazoles; Pyrimidin	2018
Novel therapies for relapsed/refractory mantle cell lymphoma. Best practice & research. Clinical haematology, 2018, Volume: 31, Issue:1 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Humans; Lymphoma, Mantle-Cell;	2018
Use of acalabrutinib in patients with mantle cell lymphoma. Expert review of hematology, 2018, Volume: 11, Issue:6 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Benzamides; Humans; Infection Control; Infections; Lym	2018
Understanding resistance mechanisms to BTK and BCL2 inhibitors in mantle cell lymphoma: implications for design of clinical trials. Leukemia & lymphoma, 2018, Volume: 59, Issue:12 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Bridged Bicyclo Compounds, Heterocyclic; Clinical Tria	2018
Maintenance Therapy in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma. Current treatment options in oncology, 2018, 07-21, Volume: 19, Issue:9 Topics: Adenine; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy P	2018
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. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2019, Volume: 25, Issue:5 Topics: Adenine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Pi	2019
Ibrutinib for Treating Relapsed or Refractory Mantle Cell Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics, 2019, Volume: 37, Issue:3 Topics: Adenine; Adult; Antineoplastic Agents; Cost-Benefit Analysis; Humans; Lymphoma, Mantle-Cell; Piperid	2019
Targeting Bruton's Tyrosine Kinase Across B-Cell Malignancies. Drugs, 2018, Volume: 78, Issue:16 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; B-Lymphocytes; Benzamides; Drug	2018
Lenalidomide for the treatment of mantle cell lymphoma. Expert opinion on pharmacotherapy, 2019, Volume: 20, Issue:5 Topics: Adenine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans;	2019
Acalabrutinib for adults with mantle cell lymphoma. Expert review of clinical pharmacology, 2019, Volume: 12, Issue:3 Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Animals; Antineoplastic Agents; Benzamides; Hum	2019
Interrogating B cell signaling pathways: A quest for novel therapies for mantle cell lymphoma. Science signaling, 2019, 02-05, Volume: 12, Issue:567 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Apoptosis; B-Lymphocytes; Humans; Lymphoma, Mantle-Cel	2019
Ibrutinib increases the risk of hypertension and atrial fibrillation: Systematic review and meta-analysis. PloS one, 2019, Volume: 14, Issue:2 Topics: Adenine; Atrial Fibrillation; Databases, Factual; Humans; Hypertension; Leukemia, Lymphocytic, Chron	2019
Bruton tyrosine kinase inhibitors for the treatment of mantle cell lymphoma: review of current evidence and future directions. Clinical advances in hematology & oncology : H&O, 2019, Volume: 17, Issue:4 Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antigens, CD20; Antineoplastic Agents; Antineoplastic	2019
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Authors	Studies
Yuan, J	1
Zhang, Q	9
Wu, S	2
Yan, S	1
Zhao, R	2
Sun, Y	7
Tian, X	2
Zhou, K	1
Stewart, CM	1
Michaud, L	1
Whiting, K	2
Nakajima, R	1
Nichols, C	2
De Frank, S	1
Hamlin, PA	2
Matasar, MJ	1
Gerecitano, JF	1
Drullinsky, P	1
Hamilton, A	1
Straus, D	1
Horwitz, SM	1
Kumar, A	2
Moskowitz, CH	1
Moskowitz, A	1
Zelenetz, AD	2
Rademaker, J	1
Salles, G	2
Seshan, V	2
Schöder, H	1
Younes, A	2
Tsui, DWY	1
Batlevi, CL	1
Portell, CA	3
Wages, NA	2
Kahl, BS	3
Budde, LE	1
Chen, RW	2
Cohen, JB	2
Varhegyi, NE	1
Petroni, GR	2