A Study Evaluating the Safety and Efficacy of Venetoclax (GDC-0199) Plus Bendamustine + Rituximab (BR) in Comparison With BR or Venetoclax Plus Rituximab in Participants With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma (fNHL)

Follicular Lymphoma Clinical Trial

Official title:

A Phase II, Open-Label Study Evaluating the Safety and Efficacy of GDC-0199 (ABT-199) Plus Bendamustine Plus Rituximab (BR) in Comparison With BR Alone or GDC-0199 Plus Rituximab (R) in Patients With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02187861
• Other study ID #: BO29337
• Secondary ID: 2014-000576-26
• Status: Completed
• Phase: Phase 2
• Start date: December 1, 2014
• Est. completion date: March 16, 2018

Study information

• Verified date: June 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, international, multicenter study will investigate the safety and efficacy of venetoclax (GDC-0199) in combination with bendamustine plus rituximab (venetoclax + BR) compared with BR alone in participants with relapsed and refractory fNHL, comparing two chemotherapy-containing regimens (Chemotherapy-Containing Cohort). In addition, an exploratory analysis of the safety and efficacy of venetoclax in combination with rituximab (venetoclax + rituximab), a chemotherapy-free regimen, will be performed (Chemotherapy-Free Cohort). Assignment to the Chemotherapy-Containing or Chemotherapy-Free Cohort will be decided at the discretion of the Investigator, unless one of the cohorts is not open to enrollment; in which case, participants may be enrolled only to the open cohort. The first 6 participants enrolled in the Chemotherapy-Containing Cohort (or more if required) will comprise the Safety Run-In group for Treatment Arm B, dosing venetoclax at 600 milligrams (mg) in combination with BR. Once a dose has been chosen from the Safety Run-In Period, randomization to the two treatment arms of the Chemotherapy-Containing Cohort (Arms B and C) will begin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: March 16, 2018
• Est. primary completion date: September 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must have histologically confirmed follicular lymphoma (FL) of Grade 1, 2, or 3a

• Participants must have received at least one prior therapy for FL

• For participants potentially receiving chemotherapy: if the participant has received prior bendamustine, response duration must have been greater than (>) 1 year

• At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

• Adequate hematologic function

• For female participants of childbearing potential and male participants with female partners of childbearing potential, agreement to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception throughout the course of study treatment and for at least 30 days after the last dose of venetoclax and 12 months after the last dose of rituximab, whichever is longer

• Confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications prior to study enrollment

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

• Contraindication to potential treatment agents

• Ongoing corticosteroid use >30 milligrams per day (mg/day) of prednisone or equivalent. Participants receiving corticosteroid treatment with less than equal to (</=) 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1)

• Primary central nervous system (CNS) lymphoma

• Vaccination with live vaccines within 28 days prior to treatment

• Chemotherapy or other investigational therapy within five half-lives of a biologic agent with a minimum of 28 days prior to the start of Cycle 1

• History of other malignancy that could affect compliance with the protocol or interpretation of results

• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the participant

• Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1

• Requires the use of warfarin

• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

• Presence of positive test results for hepatitis B surface antigen or hepatitis C virus (HCV) antibody

• Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation

• Participants with occult or prior hepatitis B virus (HBV) infection may be included if HBV deoxyribonucleic acid (DNA) is undetectable at screening. These participants must be willing to undergo monthly HBV DNA test until at least 12 months after the last treatment cycle

• Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)

• Pregnant or lactating

• Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1), other than for diagnosis

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Venetoclax
Venetoclax will be administered as per the schedule specified under arm description.
• Bendamustine
Bendamustine will be administered as per the schedule specified under arm description.
• Rituximab
Rituximab will be administered as per the schedule specified under arm description.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital; Medical Oncology	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Townsville General Hospital	Douglas	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	St George Hospital	Kogarah, New South Wales	New South Wales
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	Westmead Hospital; Haematology	Sydney	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Queen Elizabeth Hospital; Haematology	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	AZ Sint Jan	Brugge
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	British Columbia Cancer Agency	Kelowna	British Columbia
Canada	Chum Hopital Notre Dame; Centre D'Oncologie	Montreal	Quebec
Canada	Hopital Maisonneuve- Rosemont; Oncology	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Saskatoon Cancer Centre; Uni of Saskatoon Campus	Saskatoon	Saskatchewan
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
France	Institut de Cancerologie de l'Ouest	Angers
France	CHU Clermont Ferrand - Hôpital d'Estaing	Clermont Ferrand cedex 1
France	Hopital Henri Mondor	Creteil
France	CHU de Dijon - Hopital le Bocage	Dijon
France	Centre Jean Bernard	Le Mans
France	CHU Montpellier	Montpellier
France	Centre Hospitalier Lyon Sud; Hematolgie	Pierre Benite
Germany	Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III	Chemnitz
Germany	Städtisches Klinikum Dessau	Dessau-Roßlau
Germany	BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie	Dresden
Germany	Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie	Essen
Germany	Universitätsklinikum Jena; Klinik für Innere Medizin II	Jena
Germany	Universitätsklinikum Köln; Klinik I für Innere Medizin	Koeln
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie	Lübeck
Germany	Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik	Mainz
Germany	Universitätsklinikum Ulm; Apotheke	Ulm
Germany	Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie	Würzburg
Italy	Asst Papa Giovanni XXIII	Bergamo	Lombardia
Italy	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna	Bologna	Emilia-Romagna
Italy	Az. Osp. Di Careggi; Divisione Di Ematologia	Firenze	Toscana
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Ospedale Niguarda Milano	Milano	Lombardia
Italy	Irccs Policlinico San Matteo; Divisione Di Ematologia	Pavia	Lombardia
Italy	Ospedale di Ravenna	Ravenna	Emilia-Romagna
Italy	Ospedale Infermi di Rimini	Rimini	Emilia-Romagna
Italy	Azienda Ospedale San Giovanni	Torino	Piemonte
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	St James University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary; Dept. of Medical Oncology	Leicester
United Kingdom	Royal Marsden Nhs Trust; Consultant Cancer Physician	London
United Kingdom	University College London, Department of Haematology	London
United Kingdom	Christie Hospital; Breast Cancer Research Office	Manchester
United Kingdom	Churchill Hospital; Oxford Cancer and Haematology Centre	Oxford
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton
United States	Nothwest Georgia Oncology Centers P.C	Austell	Georgia
United States	Sidney Kimmel Comp Cancer Ctr	Baltimore	Maryland
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois at Chicago College of Medicine	Chicago	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Primary Healthcare Associates SC - Harvey	Harvey	Illinois
United States	UCLA School of Medicine; Hematology/Oncology	Los Angeles	California
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	West Virginia Uni Med. Center - Robert Byrd Health Science	Morgantown	West Virginia
United States	University of Pennsylvania; School of Medicine	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	James P. Wilmot Cancer Center	Rochester	New York
United States	Arizona Cancer Center	Tucson	Arizona
United States	University of Kansas; Medical Center & Medical pavilion	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as Per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)	CMR: a score 1 (no uptake above background), 2 (uptake less than or equal to [<=] mediastinum), or 3 (uptake less than [<] mediastinum but <=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites with no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.	6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)
Secondary	Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA	CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (	4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1	CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (uptake	48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1	CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (	48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan	CR: defined as reduction of longest transverse diameter of lesion (LDi) of target nodes/nodal masses to <=1.5 centimeters (cm), and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.	6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan	CR: defined as reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.	4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan	OR was defined as CMR or Partial Metabolic Response (PMR). CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (	6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan	OR was defined as CMR or PMR. CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (	4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan	OR was defined as CR or Partial Response (PR). CR: reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: greater than or equal to (>=) 50 percent (%) decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least >50% beyond normal; and no new lesions. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.	6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan	OR was defined as CR or PR. CR: reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: >=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least >50% beyond normal; and no new lesions. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.	4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary	Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan	OR was defined as CMR/CR or PMR/PR. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing).	Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary	Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan	DOR was defined as time from CMR/CR or PMR/PR until progressive disease (PD) or death due to any cause. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing). DOR was calculated using Kaplan-Meier method.	From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary	Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death	PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.	Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary	Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan	PFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) until the date of disease progression, or death due to any cause. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. PFS was calculated using Kaplan-Meier method.	Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary	Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy	PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.	Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)
Secondary	Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan	EFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to the date of disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. EFS was calculated using Kaplan-Meier method.	Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)
Secondary	Percentage of Participants Who Died Due to Any Cause		Baseline until death due to any cause (assessed up to approximately 2.5 years
Secondary	Overall Survival (OS)	OS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to death due to any cause. For participants who are alive, OS was censored at the last contact. OS was calculated using Kaplan-Meier method.	Baseline until death due to any cause (assessed up to approximately 2.5 years)
Secondary	Apparent Clearance (CL) of Venetoclax	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Secondary	Apparent Volume of Distribution (Vd) of Venetoclax	Vd was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Secondary	Time to Maximum Plasma Concentration (Tmax) of Venetoclax		Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Secondary	Maximum Plasma Concentration (Cmax) of Venetoclax		Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax	Area under the plasma concentration versus time curve from zero to the last measured concentration (AUClast).	Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Secondary	Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax	Area under the plasma concentration versus time curve from time 0 (pre-dose) to 8 hours post dose (AUC0-8h).	Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)