Page last updated: 2024-10-16

adenine and Minimal Disease, Residual

adenine has been researched along with Minimal Disease, Residual in 30 studies

Research Excerpts

ExcerptRelevanceReference
" We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients."3.11Ibrutinib 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)
"After minimal residual disease-guided treatment (day 1 of month 16), 84 (62%, 90% CI 55-69) of 135 patients (ITT population) achieved a complete response with bone marrow minimal residual disease of less than 0·01%."2.90Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial. ( Aanei, C; Aurran, T; Banos, A; Carassou, P; Cartron, G; Cymbalista, F; Dartigeas, C; de Guibert, S; Delmer, A; Dilhuydy, MS; Feugier, P; Fornecker, LM; Laribi, K; Le Garff-Tavernier, M; Leblond, V; Lepretre, S; Letestu, R; Lévy, V; Mahe, B; Michallet, AS; Nguyen-Khac, F; Orsini, F; Pegourie, B; Portois, C; Rouille, V; Salles, G; Subtil, F; Ticchioni, M; Tomowiak, C; Tournilhac, O; Truchan Graczyk, M; Villemagne, B; Vilque, JP; Ysebaert, L, 2019)
"Advances in the molecular biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and development of molecularly targeted therapies have resulted in treatment innovations."2.66Evolution in the management of chronic lymphocytic leukemia in Japan: should MRD negativity be the goal? ( Suzumiya, J; Takizawa, J, 2020)

Research

Studies (30)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's12 (40.00)24.3611
2020's18 (60.00)2.80

Authors

AuthorsStudies
Wierda, WG6
Allan, JN3
Siddiqi, T2
Kipps, TJ2
Opat, S2
Tedeschi, A3
Badoux, XC1
Kuss, BJ2
Jackson, S2
Moreno, C2
Jacobs, R3
Pagel, JM1
Flinn, I1
Pak, Y1
Zhou, C3
Szafer-Glusman, E2
Ninomoto, J3
Dean, JP2
James, DF1
Ghia, P3
Tam, CS4
Giné, E1
de la Cruz, F1
Jiménez Ubieto, A1
López Jimenez, J1
Martín García-Sancho, A1
Terol, MJ1
González Barca, E1
Casanova, M1
de la Fuente, A1
Marín-Niebla, A1
Muntañola, A1
González-López, TJ1
Aymerich, M1
Setoain, X1
Cortés-Romera, M1
Rotger, A1
Rodríguez, S1
Medina Herrera, A1
García Sanz, R1
Nadeu, F1
Beà, S1
Campo, E1
López-Guillermo, A1
Huber, H1
Edenhofer, S1
von Tresckow, J1
Robrecht, S1
Zhang, C1
Tausch, E1
Schneider, C1
Bloehdorn, J1
Fürstenau, M2
Dreger, P2
Ritgen, M1
Illmer, T1
Illert, AL1
Dürig, J1
Böttcher, S2
Niemann, CU2
Kneba, M2
Fink, AM2
Fischer, K1
Döhner, H2
Hallek, M3
Eichhorst, B2
Stilgenbauer, S2
Barr, PM3
Trentin, L1
Bannerji, R1
Russell, K1
Kater, AP1
Levin, MD1
Dubois, J1
Kersting, S1
Enggaard, L1
Veldhuis, GJ1
Mous, R1
Mellink, CHM1
van der Kevie-Kersemaekers, AF1
Dobber, JA1
Poulsen, CB1
Frederiksen, H1
Janssens, A1
Schjødt, I1
Dompeling, EC1
Ranti, J1
Brieghel, C1
Mattsson, M1
Bellido, M1
Tran, HTT1
Nasserinejad, K1
Roeker, LE1
Feldman, TA1
Soumerai, JD1
Falco, V1
Panton, G1
Dorsey, C1
Zelenetz, AD1
Falchi, L1
Park, JH1
Straus, DJ1
Pena Velasquez, C1
Lebowitz, S1
Fox, Y1
Battiato, K1
Laudati, C1
Thompson, MC1
McCarthy, E1
Kdiry, S1
Martignetti, R1
Turpuseema, T1
Purdom, M1
Paskalis, D1
Miskin, HP1
Sportelli, P1
Leslie, LA1
Mato, AR3
Vallisa, D1
O'Brien, S4
Grigg, AP1
Walker, P1
Krigsfeld, G1
Thompson, PA2
Keating, MJ4
Ferrajoli, A4
Jain, N4
Peterson, CB1
Garg, N2
Wang, SA1
Jorgensen, JL1
Kadia, TM1
Bose, P2
Pemmaraju, N2
Short, NJ1
Huang, SJ1
Gerrie, AS1
Young, S1
Tucker, T1
Bruyere, H1
Hrynchak, M1
Galbraith, P1
Al Tourah, AJ1
Dueck, G1
Noble, MC1
Ramadan, KM1
Tsang, P1
Hardy, E1
Sehn, L1
Toze, CL1
Suzumiya, J1
Takizawa, J1
Gianfelici, V1
Levato, L1
Molica, S1
Hu, EY1
Blachly, JS1
Saygin, C1
Ozer, HG1
Workman, SE1
Lozanski, A1
Doong, TJ1
Chiang, CL1
Bhat, S1
Rogers, KA2
Woyach, JA2
Coombes, KR1
Jones, D1
Muthusamy, N1
Lozanski, G2
Byrd, JC3
Huang, Y1
Ruppert, AS1
Abruzzo, LV1
Andersen, BL1
Awan, FT1
Bhat, SA1
Dean, A1
Lucas, M1
Banks, C1
Grantier, C1
Heerema, NA1
Maddocks, KJ1
Valentine, TR1
Weiss, DM1
Jones, JA1
Michallet, AS2
Letestu, R2
Le Garff-Tavernier, M2
Aanei, C2
Ticchioni, M2
Dilhuydy, MS2
Subtil, F2
Rouille, V2
Mahe, B2
Laribi, K2
Villemagne, B2
Salles, G2
Tournilhac, O2
Delmer, A2
Portois, C2
Pegourie, B2
Leblond, V2
Tomowiak, C2
De Guibert, S2
Orsini Piocelle, F1
Banos, A2
Carassou, P2
Cartron, G3
Fornecker, LM2
Ysebaert, L2
Dartigeas, C2
Truchan-Graczyk, M1
Vilque, JP2
Aurran, T2
Cymbalista, F2
Lepretre, S2
Levy, V2
Nguyen-Khac, F2
Feugier, P2
Le Gouill, S1
Morschhauser, F1
Chiron, D1
Bouabdallah, K1
Casasnovas, O1
Bodet-Milin, C1
Ragot, S1
Bossard, C1
Nadal, N1
Herbaux, C1
Tessoulin, B1
Tchernonog, E1
Rossi, C1
McCulloch, R1
Gastinne, T1
Callanan, MB1
Rule, S1
Lu, P1
Wang, S1
Franzen, CA1
Venkataraman, G1
McClure, R1
Li, L1
Wu, W1
Niu, N1
Sukhanova, M1
Pei, J1
Baldwin, DA1
Nejati, R1
Wasik, MA1
Khan, N1
Tu, Y1
Gao, J1
Chen, Y1
Ma, S1
Larson, RA1
Wang, YL1
Cheson, BD1
Wang, XV1
Hanson, CA1
Tschumper, RC1
Lesnick, CE1
Braggio, E1
Paietta, EM1
Barrientos, JC1
Leis, JF1
Zhang, CC1
Coutre, SE2
Cashen, AF1
Singh, AK1
Mullane, MP1
Erba, H1
Stone, R1
Litzow, MR1
Tallman, MS1
Shanafelt, TD1
Kay, NE1
Winqvist, M1
Palma, M1
Heimersson, K1
Mellstedt, H1
Österborg, A1
Lundin, J1
Krämer, I1
Dietrich, S1
Zeis, M1
Stadler, M1
Bittenbring, J1
Uharek, L1
Scheid, C1
Hegenbart, U1
Ho, A1
Schmitz, N1
Collett, L1
Howard, DR1
Munir, T1
McParland, L1
Oughton, JB1
Rawstron, AC1
Hockaday, A1
Dimbleby, C1
Phillips, D1
McMahon, K1
Hulme, C1
Allsup, D1
Bloor, A1
Hillmen, P2
Anderson, MA1
Pott, C1
Agarwal, R1
Handunnetti, S1
Hicks, RJ1
Burbury, K1
Turner, G1
Di Iulio, J1
Bressel, M1
Westerman, D1
Lade, S1
Dreyling, M1
Dawson, SJ1
Dawson, MA1
Seymour, JF1
Roberts, AW1
Burger, JA2
Sivina, M1
Kim, E1
Kadia, T2
Estrov, Z3
Nogueras-Gonzalez, GM1
Huang, X1
Jorgensen, J2
Li, J1
Cheng, M1
Clow, F2
Ohanian, M2
Andreeff, M1
Mathew, T1
Thompson, P2
Kantarjian, H2
Keating, M1
Burger, J1
Borthakur, G1
Takahashi, K1
Fowler, N1
Konopleva, M1
Alvarado, Y1
Yilmaz, M1
DiNardo, C1
Jabbour, E1
Sasaki, K1
Kanagal-Shamanna, R1
Patel, K1
Wang, X2
Sondermann, K1
Cruz, N1
Wei, C1
Ayala, A1
Plunkett, W1
Gandhi, V1
Wierda, W1
Orsini, F1
Truchan Graczyk, M1
O'Brien, SM1
Xiao, L1
Ryan, CE1
Sahaf, B1
Logan, AC1
Brown, JR1
Dyer, MJ1
Jaglowski, S1
Rezvani, AR1
Styles, L1
Miklos, DB1

Clinical Trials (10)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma[NCT02910583]Phase 2323 participants (Actual)Interventional2016-09-28Active, 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 250 participants (Anticipated)Interventional2016-05-18Active, not recruiting
A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations[NCT03226301]Phase 2230 participants (Anticipated)Interventional2017-06-23Active, not recruiting
Obinutuzumab, Ibrutinib, and Venetoclax for Relapsed and Previously Untreated Chronic Lymphocytic Leukemia (CLL)[NCT02427451]Phase 1/Phase 287 participants (Actual)Interventional2015-08-03Active, not recruiting
"Phase II, Multicenter, Trial, Exploring Chemo-free Treatment (GA101+Ibrutinib) and MRD-driven Strategy in Previously Untreated Symptomatic B-chronic Lymphocytic Leukemia Medically Fit A Study From the Goelams/GCFLLC/MW Intergroup"[NCT02666898]Phase 2135 participants (Actual)Interventional2015-10-31Completed
A Phase I/II Trial of Obinutuzumab, ABT-199 (GDC-0199) Plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma Patients[NCT02558816]Phase 1/Phase 248 participants (Actual)Interventional2015-10-14Active, not recruiting
Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia[NCT00281983]Phase 1/Phase 2100 participants (Actual)Interventional2000-06-30Completed
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 237 participants (Actual)Interventional2015-07-22Active, not recruiting
Ibrutinib vs Ibrutinib + Rituximab (i vs iR) in Patients With Relapsed (CLL)[NCT02007044]Phase 2208 participants (Anticipated)Interventional2013-12-06Active, not recruiting
A Phase II Study of Venetoclax and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL)[NCT02756897]Phase 2234 participants (Actual)Interventional2016-07-07Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

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

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

Interventionpercentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated55.9
FD Cohort: All Treated55.3

FD Cohort: DOR

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

Interventionpercentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated96.1
FD Cohort: All Treated94.7

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

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

Interventionpercentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated97.7
FD Cohort: All Treated98.1

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

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

Interventionpercentage of participants (Median)
FD Cohort, Non-Del 17p Population: All Treated96.2
FD Cohort: All Treated94.8

FD Cohort: ORR

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

Interventionpercentage of participants (Number)
FD Cohort, Non-Del 17p Population: All Treated95.6
FD Cohort: All Treated96.2

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

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

Interventionpercentage of participants (Number)
FD Cohort: All Treated94.1

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

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

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

MRD Cohort: CRR (CR/CRi Rate)

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated62.8
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)72.1
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)60.5
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib74.2
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax56.3

MRD Cohort: Duration of Response (DOR)

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated94.7
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)95.3
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax96.7

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

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated99.4
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax100.0

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

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated95.6
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)95.3
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib96.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax96.7

MRD Cohort: Overall Response Rate (ORR)

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated97.0
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)100.0
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib100.0
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax100.0

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

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

Interventionng/mL (Geometric Mean)
MRD Cohort: All Treated88.5

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

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

InterventionL/h (Geometric Mean)
MRD Cohort: All Treated833

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

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

Intervention1/h (Geometric Mean)
MRD Cohort: All Treated0.132

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

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

Interventionng*h/mL (Geometric Mean)
MRD Cohort: All Treated48993

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

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

InterventionL/h (Geometric Mean)
MRD Cohort: All Treated8.16

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

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

Interventionng/mL (Geometric Mean)
MRD Cohort: All Treated3034

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

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

Interventionhours (Median)
MRD Cohort: All Treated6.00

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

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

Interventionpercentage of participants (Number)
MRD Cohort: All Treated90.0

FD Cohort: MRR

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

,
Interventionpercentage of participants (Number)
BM or PBBMPB
FD Cohort, Non-Del 17p Population: All Treated78.761.876.5
FD Cohort: All Treated78.659.776.7

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

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

Interventionpercentage of participants (Number)
Any TEAEAny Grade >=3 TEAEAny Ibrutinib (Ibr)-Related TEAEAny Grade >=3 Ibrutinib-Related TEAEAny Venetoclax (Ven)-Related TEAEAny Grade >=3 Venetoclax-Related TEAEAny TEAE Leading to Ibr or Ven DiscontinuationAny TEAE Leading to Ibr or Ven Discontinuation: Ibr OnlyAny TEAE Leading to Ibr or Ven Discontinuation: Ven OnlyAny TEAE Leading to Ibr or Ven Discontinuation: Both Ibr and VenAny TEAE Leading to Ibr or Ven Dose ReductionAny TEAE Leading to Ibr Only Dose ReductionAny TEAE Leading to Ven Only Dose ReductionAny TEAE Leading to Both Ibr and Ven Dose ReductionAny SAEAny Grade >= 3 SAEAny SAE Related to Ibr or VenAny Ibr-related SAEAny Ven-related SAEFatal TEAEMajor Hemorrhage TEAEGrade >= 3 Major Hemorrhage TEAEMajor Hemorrhage SAE
FD Cohort: All Treated99.462.392.544.784.344.75.03.101.920.85.711.33.822.619.513.211.38.20.61.91.31.3

MRD Cohort: MRD-Negativity Rate (MRR)

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

,,,
Interventionpercentage of participants (Number)
PB or BMBMPB
MRD Cohort: All Treated81.176.879.3
MRD Cohort/uMRD Not Confirmed: All Participants63.554.058.7
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib51.641.948.4
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax75.065.668.8

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

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

,,,,
Interventionpercentage of participants (Number)
Any TEAEAny Grade >=3 TEAEAny Ibrutinib (Ibr)-Related TEAEAny Grade >=3 Ibrutinib-Related TEAEAny Venetoclax (Ven)-Related TEAEAny Grade >=3 Venetoclax-Related TEAEAny TEAE Leading to Ibr or Ven DiscontinuationAny TEAE Leading to Ibr or Ven Discontinuation: Ibr OnlyAny TEAE Leading to Ibr or Ven Discontinuation: Ven OnlyAny TEAE Leading to Ibr or Ven Discontinuation: Both Ibr and VenAny TEAE Leading to Ibr or Ven Dose ReductionAny TEAE Leading to Ibr Only Dose ReductionAny TEAE Leading to Ven Only Dose ReductionAny TEAE Leading to Both Ibr and Ven Dose ReductionAny SAEAny Grade >= 3 SAEAny SAE Related to Ibr or VenAny Ibr-related SAEAny Ven-related SAEFatal TEAEMajor Hemorrhage TEAEGrade >= 3 Major Hemorrhage TEAEMajor Hemorrhage SAE
MRD Cohort: All Treated100.073.894.557.980.544.512.87.31.24.324.414.65.54.331.126.218.315.95.50.62.41.82.4
MRD Cohort/Confirmed uMRD: Randomized to Ibrutinib (Blinded)100.079.193.055.886.051.24.72.32.3020.914.04.72.327.925.616.311.64.702.32.32.3
MRD Cohort/Confirmed uMRD: Randomized to Placebo (Blinded)100.065.193.048.876.734.9000023.39.311.62.318.616.311.69.37.00000
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib100.071.096.861.380.645.29.79.70022.616.106.535.529.022.619.49.73.23.23.23.2
MRD Cohort/uMRD Not Confirmed: Randomized to Open-Label Ibrutinib + Venetoclax100.075.093.862.596.956.312.53.109.431.321.93.16.337.528.118.818.83.106.33.16.3

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

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

Interventionng*h/mL (Geometric Mean)
AUC0-24hAUClast
MRD Cohort: All Treated504480

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

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

Interventionhours (Median)
tmaxtlastt1/2term
MRD Cohort: All Treated2.0024.05.30

Reviews

2 reviews available for adenine and Minimal Disease, Residual

ArticleYear
Evolution in the management of chronic lymphocytic leukemia in Japan: should MRD negativity be the goal?
    International journal of hematology, 2020, Volume: 111, Issue:5

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Bridged Bicyclo Compou

2020
The Evolution of Targeted Therapies in Chronic Lymphocytic Leukaemia.
    Current hematologic malignancy reports, 2020, Volume: 15, Issue:4

    Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Humans; Leukemia, Lymphocytic,

2020

Trials

17 trials available for adenine and Minimal Disease, Residual

ArticleYear
Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021, 12-01, Volume: 39, Issue:34

    Topics: Adenine; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Het

2021
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2022, 04-10, Volume: 40, Issue:11

    Topics: Adenine; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Lymphoma, Mantle-Cell;

2022
Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia.
    Blood, 2022, 03-03, Volume: 139, Issue:9

    Topics: Adenine; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined

2022
Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial.
    The Lancet. Oncology, 2022, Volume: 23, Issue:6

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Hu

2022
Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2022, 09-15, Volume: 28, Issue:18

    Topics: Adenine; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Heterocyclic Compou

2022
Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020, 11-01, Volume: 38, Issue:31

    Topics: Adenine; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protoc

2020
A fixed-duration, measurable residual disease-guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial.
    Blood, 2021, 02-25, Volume: 137, Issue:8

    Topics: Adenine; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Com

2021
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial.
    Blood, 2021, 02-18, Volume: 137, Issue:7

    Topics: Adenine; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemoth

2021
Measurable residual disease does not preclude prolonged progression-free survival in CLL treated with ibrutinib.
    Blood, 2021, 12-30, Volume: 138, Issue:26

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia,

2021
Dual targeting of Bruton tyrosine kinase and CD52 induces minimal residual disease-negativity in the bone marrow of poor-prognosis chronic lymphocytic leukaemia patients but is associated with opportunistic infections - Results from a phase I study.
    British journal of haematology, 2018, Volume: 182, Issue:4

    Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Alemtuzumab; Antineoplastic Combined Chemotherap

2018
Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial.
    Blood, 2017, 09-21, Volume: 130, Issue:12

    Topics: Adenine; Adult; Aged; Alemtuzumab; Allografts; Antineoplastic Agents, Immunological; Combined Modali

2017
Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial.
    Trials, 2017, 08-22, Volume: 18, Issue:1

    Topics: Adenine; Adolescent; Adult; Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chem

2017
Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma.
    The New England journal of medicine, 2018, 03-29, Volume: 378, Issue:13

    Topics: Adenine; Administration, Oral; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Antineo

2018
Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia.
    Blood, 2019, 03-07, Volume: 133, Issue:10

    Topics: Adenine; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Antineoplastic Combin

2019
Ibrutinib and Venetoclax for First-Line Treatment of CLL.
    The New England journal of medicine, 2019, 05-30, Volume: 380, Issue:22

    Topics: Adenine; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy

2019
Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial.
    The Lancet. Haematology, 2019, Volume: 6, Issue:9

    Topics: Adenine; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Dr

2019
Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT.
    Blood, 2016, 12-22, Volume: 128, Issue:25

    Topics: Adenine; Adult; Aged; B-Lymphocytes; Chimerism; Cohort Studies; Female; Germinal Center; Graft vs Ho

2016

Other Studies

11 other studies available for adenine and Minimal Disease, Residual

ArticleYear
Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort.
    Blood, 2022, 06-02, Volume: 139, Issue:22

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Hu

2022
Effective Tumor Debulking with Ibrutinib Before Initiation of Venetoclax: Results from the CAPTIVATE Minimal Residual Disease and Fixed-Duration Cohorts.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2022, 10-14, Volume: 28, Issue:20

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Cr

2022
Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD.
    Leukemia, 2023, Volume: 37, Issue:7

    Topics: Adenine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Hu

2023
Highlights in chronic lymphocytic leukemia from the 60th American Society of Hematology Annual Meeting.
    Clinical advances in hematology & oncology : H&O, 2019, Volume: 17 Suppl 1, Issue:1

    Topics: Adenine; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Chloramb

2019
Relapsed disease and aspects of undetectable MRD and treatment discontinuation.
    Hematology. American Society of Hematology. Education Program, 2019, 12-06, Volume: 2019, Issue:1

    Topics: Adenine; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bridged Bicyclo Co

2019
Comparison of real-world treatment patterns in chronic lymphocytic leukemia management before and after availability of ibrutinib in the province of British Columbia, Canada.
    Leukemia research, 2020, Volume: 91

    Topics: Adenine; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; British Col

2020
LC-FACSeq is a method for detecting rare clones in leukemia.
    JCI insight, 2020, 06-18, Volume: 5, Issue:12

    Topics: Adenine; Clonal Evolution; Clone Cells; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Mu

2020
Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.
    Blood cancer journal, 2021, 02-18, Volume: 11, Issue:2

    Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Antineoplastic Agents;

2021
A clinical perspective on minimal residual disease (MRD) assessment in chronic lymphocytic leukemia.
    Clinical advances in hematology & oncology : H&O, 2020, Volume: 18 Suppl 10, Issue:6

    Topics: Adenine; Adult; Age Factors; Aged; Aged, 80 and over; Disease-Free Survival; Female; Flow Cytometry;

2020
Is chemoimmunotherapy maintenance of value in patients with chronic lymphocytic leukaemia and minimal residual disease?
    The Lancet. Haematology, 2019, Volume: 6, Issue:9

    Topics: Adenine; Antibodies, Monoclonal, Humanized; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm

2019
β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.
    Cancer, 2016, Feb-15, Volume: 122, Issue:4

    Topics: Adenine; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bendamustin

2016