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Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) (Captivate)

Primary Purpose

Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ibrutinib

venetoclax

Placebo

About this trial

This is an interventional treatment trial for Leukemia

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of CLL/SLL that meets 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria (Hallek et al), with active disease meeting at least 1 IWCLL criteria for requiring treatment.
Measurable nodal disease by computed tomography (CT)
Adequate hepatic, and renal function
Adequate hematologic function
absolute neutrophil count >750/µL
platelet count >30,000 /μL
hemoglobin >8.0 g/dL

Exclusion Criteria:

Any prior therapy used for treatment of CLL/SLL
Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome (TLS)

Sites / Locations

City of Hope /ID# 1142-0047
Moores Cancer Center at UC San Diego /ID# 1142-0241
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1142-0008
Norton Cancer Center /ID# 1142-0071
Rutgers Cancer Institute of New Jersey /ID# 1142-1193
Northwell Health/Long Island Jewish Hospital /ID# 1142-0350
New York Presbyterian Hospital/Weill Cornell Med College /ID# 1142-0200
University of Rochester Cancer Center /ID# 1142-0127
Charlotte-Mecklenberg Hospital, Carolinas Healthcare System, Levine Cancer Inst /ID# 1142-0733
Cleveland Clinic Foundation /ID# 1142-0739
University of Pennsylvania /ID# 1142-0069
Tennessee Oncology - Chattanooga /ID# 1142-0123
MD Anderson Cancer Center /ID# 1142-0032
Swedish Cancer Institute /ID# 1142-0114
St George Hospital /ID# 1142-0654
Flinders Medical Centre /ID# 1142-0163
Monash Medical Centre /ID# 1142-0556
Peter MacCallum Cancer Centre-East Melbourne /ID# 1142-0633
St Vincent's Hospital Melbourne /ID# 1142-0501
Frankston Hospital /ID# 1142-0715
Austin Health /ID# 1142-0170
Ospedale San Raffaele IRCCS /ID# 1142-0523
Ospedale Policlinico San Martino /ID# 1142-0903
ASST Grande Ospedale Metropolitano Niguarda /ID# 1142-0581
Azienda Ospedaliero-Universitaria di Modena /ID# 1142-0524
Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1142-0582
Azienda Ospedaliera di Padova /ID# 1142-1175
Azienda USL di Piacenza - Ospedale Guglielmo da Saliceto /ID# 1142-1182
Middlemore Hospital /ID# 1142-0662
Christchurch Hospital /ID# 1142-0589
Palmerston North Hospital /ID# 1142-0585
North Shore Hospital /ID# 1142-0663
Duplicate_Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie /ID# 1142-0590
Malopolskie Centrum Medyczne /ID# 1142-0364
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1142-0592
Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1142-0529
Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1142-0531
Hospital Duran i Reynals /ID# 1142-0604
Hospital Universitario Puerta de Hierro, Majadahonda /ID# 1142-0536
Complejo Hospitalario de Navarra /ID# 1142-1197
Hospital Clinic de Barcelona /ID# 1142-0533
Hospital Santa Creu i Sant Pau /ID# 1142-0535
Hospital Universitario Virgen de las Nieves /ID# 1142-1196
Hospital Universitario Ramon y Cajal /ID# 1142-0874
Hospital Universitario 12 de Octubre /ID# 1142-0864
Hospital Clinico Universitario de Salamanca /ID# 1142-0790

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax

MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)

MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)

MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)

Arm Description

Participants receive 420 mg of single-agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity. After MRD-positive relapse or disease progression (PD) by iwCLL criteria, participants can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity. If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

FD Cohort: MRR

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.

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

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

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.

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

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)

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)

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

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

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

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

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

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

Full Information

NCT ID

NCT02910583

First Posted

September 20, 2016

Last Updated

April 13, 2023

Sponsor

Pharmacyclics LLC.

Collaborators

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02910583

Brief Title

Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)

Acronym

Captivate

Official Title

Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 28, 2016 (Actual)

Primary Completion Date

November 12, 2020 (Actual)

Study Completion Date

March 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pharmacyclics LLC.

Collaborators

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multicenter, 2-cohort Phase 2 study assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Participants with confirmed undetectable minimal residual disease (uMRD) in the MRD cohort are triple masked. Allocation was not randomized for the Fixed Duration (FD) cohort.

Allocation

Randomized

Enrollment

323 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax

Arm Type

Experimental

Arm Description

Arm Title

MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)

Arm Type

Experimental

Arm Description

Arm Title

MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)

Arm Type

Placebo Comparator

Arm Description

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity. If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Arm Title

MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

Arm Type

Experimental

Arm Description

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Arm Title

MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ibrutinib

Intervention Description

ibrutinib administered orally once daily (three 140 mg capsules)

Intervention Type

Drug

Intervention Name(s)

venetoclax

Intervention Description

venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo capsules to match ibrutinib administered orally once daily

Primary Outcome Measure Information:

Title

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

Description

Time Frame

1 year after randomization

Title

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

Description

Time Frame

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.

Secondary Outcome Measure Information:

Title

MRD Cohort: CRR (CR/CRi Rate)

Description

Time Frame

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).

Title

MRD Cohort: Overall Response Rate (ORR)

Description

Time Frame

Title

MRD Cohort: Duration of Response (DOR)

Description

Time Frame

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).

Title

MRD Cohort: MRD-Negativity Rate (MRR)

Description

Time Frame

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).

Title

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)

Description

Time Frame

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).

Title

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

Description

Time Frame

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).

Title

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

Description

Time Frame

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).

Title

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

Description

Time Frame

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.

Title

FD Cohort: ORR

Description

Time Frame

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.

Title

FD Cohort: DOR

Description

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.

Time Frame

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).

Title

FD Cohort: MRR

Description

Time Frame

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).

Title

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

Description

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.

Time Frame

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).

Title

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

Description

Time Frame

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).

Title

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

Description

Time Frame

Title

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

Description

Time Frame

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.

Title

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

Time Frame