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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02187861




Registration number
NCT02187861
Ethics application status
Date submitted
9/07/2014
Date registered
11/07/2014
Date last updated
5/06/2019

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2014-000576-26
Secondary ID [2] 0 0
BO29337
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Bendamustine
Treatment: Drugs - Rituximab

Experimental: Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) - Participants will receive venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in will continue until first 9 participants complete the safety observation window of 28 days. Participants will continue receiving the same treatment as decided for Arm B.

Experimental: Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) - Participants will receive venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m\^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle will be of 28 days.

Experimental: Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) - Participants will receive venetoclax at doses decided from safety run-in orally once daily continuously for 1 year along with rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Active comparator: Chemotherapy-Containing Cohort: Arm C (BR) - Participants will receive rituximab 375 mg/m\^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m\^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.


Treatment: Drugs: Venetoclax
Venetoclax will be administered as per the schedule specified under arm description.

Treatment: Drugs: Bendamustine
Bendamustine will be administered as per the schedule specified under arm description.

Treatment: Drugs: Rituximab
Rituximab will be administered as per the schedule specified under arm description.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)
Secondary outcome [1] 0 0
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA
Timepoint [1] 0 0
4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)
Secondary outcome [2] 0 0
Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1
Timepoint [2] 0 0
48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [3] 0 0
Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1
Timepoint [3] 0 0
48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [4] 0 0
Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan
Timepoint [4] 0 0
6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [5] 0 0
Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan
Timepoint [5] 0 0
4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [6] 0 0
Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan
Timepoint [6] 0 0
6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [7] 0 0
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan
Timepoint [7] 0 0
4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [8] 0 0
Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan
Timepoint [8] 0 0
6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [9] 0 0
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan
Timepoint [9] 0 0
4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)
Secondary outcome [10] 0 0
Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan
Timepoint [10] 0 0
Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary outcome [11] 0 0
Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan
Timepoint [11] 0 0
From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary outcome [12] 0 0
Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death
Timepoint [12] 0 0
Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary outcome [13] 0 0
Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan
Timepoint [13] 0 0
Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)
Secondary outcome [15] 0 0
Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan
Timepoint [15] 0 0
Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)
Secondary outcome [16] 0 0
Percentage of Participants Who Died Due to Any Cause
Timepoint [16] 0 0
Baseline until death due to any cause (assessed up to approximately 2.5 years
Secondary outcome [17] 0 0
Overall Survival (OS)
Timepoint [17] 0 0
Baseline until death due to any cause (assessed up to approximately 2.5 years)
Secondary outcome [18] 0 0
Apparent Clearance (CL) of Venetoclax
Timepoint [18] 0 0
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 outcome [19] 0 0
Apparent Volume of Distribution (Vd) of Venetoclax
Timepoint [19] 0 0
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 outcome [20] 0 0
Time to Maximum Plasma Concentration (Tmax) of Venetoclax
Timepoint [20] 0 0
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 outcome [21] 0 0
Maximum Plasma Concentration (Cmax) of Venetoclax
Timepoint [21] 0 0
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 outcome [22] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax
Timepoint [22] 0 0
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 outcome [23] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax
Timepoint [23] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital; Medical Oncology - Camperdown
Recruitment hospital [2] 0 0
St George Hospital - Kogarah, New South Wales
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [4] 0 0
Westmead Hospital; Haematology - Sydney
Recruitment hospital [5] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [6] 0 0
Townsville General Hospital - Douglas
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 0 0
Queen Elizabeth Hospital; Haematology - Woodville South
Recruitment hospital [9] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [10] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah, New South Wales
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
2145 - Sydney
Recruitment postcode(s) [5] 0 0
2298 - Waratah
Recruitment postcode(s) [6] 0 0
4184 - Douglas
Recruitment postcode(s) [7] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 0 0
5011 - Woodville South
Recruitment postcode(s) [9] 0 0
7000 - Hobart
Recruitment postcode(s) [10] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
West Virginia
Country [13] 0 0
Belgium
State/province [13] 0 0
Antwerpen
Country [14] 0 0
Belgium
State/province [14] 0 0
Brugge
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Canada
State/province [20] 0 0
Saskatchewan
Country [21] 0 0
France
State/province [21] 0 0
Angers
Country [22] 0 0
France
State/province [22] 0 0
Clermont Ferrand cedex 1
Country [23] 0 0
France
State/province [23] 0 0
Creteil
Country [24] 0 0
France
State/province [24] 0 0
Dijon
Country [25] 0 0
France
State/province [25] 0 0
Le Mans
Country [26] 0 0
France
State/province [26] 0 0
Montpellier
Country [27] 0 0
France
State/province [27] 0 0
Pierre Benite
Country [28] 0 0
Germany
State/province [28] 0 0
Chemnitz
Country [29] 0 0
Germany
State/province [29] 0 0
Dessau-Roßlau
Country [30] 0 0
Germany
State/province [30] 0 0
Dresden
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
Country [32] 0 0
Germany
State/province [32] 0 0
Jena
Country [33] 0 0
Germany
State/province [33] 0 0
Koeln
Country [34] 0 0
Germany
State/province [34] 0 0
Lübeck
Country [35] 0 0
Germany
State/province [35] 0 0
Mainz
Country [36] 0 0
Germany
State/province [36] 0 0
Ulm
Country [37] 0 0
Germany
State/province [37] 0 0
Würzburg
Country [38] 0 0
Italy
State/province [38] 0 0
Emilia-Romagna
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardia
Country [40] 0 0
Italy
State/province [40] 0 0
Piemonte
Country [41] 0 0
Italy
State/province [41] 0 0
Toscana
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Blackpool
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Leeds
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Leicester
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Manchester
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Oxford
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.