A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Part of paid clinical trials in La Jolla, California.

Sponsor
Hoffmann-La Roche
Study ID
NCT02005471
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Bendamustine — DRUG
    Bendamustine will be administered at a dose of 70 mg/m\^2 via IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
  • Venetoclax — DRUG
    Venetoclax will be administered at an initial dose of 20 mg via tablet orally QD, incremented weekly up to a maximum dose of 400 mg during a 5-week ramp-up period. Venetoclax will be continued at 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurs first. R/C Substudy: venetoclax will be administered for 5-week dose ramp-up period to reach the target dose of 400 mg QD. Venetoclax will continue to be administered during the rituximab cycles until disease progression or for a maximum of 2 years from Cycle 1R/C Day 1 of the R/C Substudy.
  • Rituximab — DRUG
    Rituximab will be administered at a dose of 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m\^2 on Day 1 of Cycles 2-6. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.

Study Details

The purpose of this open-label, multicenter, randomized, Phase III study is to evaluate the benefit of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in participants with relapsed or refractory CLL. Participants will be randomly assigned in 1:1 ratio to receive either venetoclax + rituximab (Arm A) or bendamustine + rituximab (Arm B).

Key Dates

Start date
Mar 17, 2014
Status verified
Sep 2023
Primary completion
May 8, 2017
Completion
Aug 3, 2022

Study Design

Enrollment
389 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Bendamustine + Rituximab
    Participants will receive bendamustine 70 milligrams per meter square (mg/m\^2) via intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.
  • Experimental: Venetoclax + Rituximab
    Participants will be initially placed on a venetoclax 5 weeks ramp-up period, and will receive an initial dose of 20 milligrams (mg) via tablet orally once daily (QD). Then the dose will be incremented weekly up to a maximum dose of 400 mg. Participants will then continue receiving venetoclax 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards, as directed by the investigator, in combination with rituximab 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.
  • Experimental: Bendamustine + Rituximab Crossover Substudy
    Participants entering the Crossover Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Crossover Day 1 of the Substudy.
  • Experimental: Venetoclax + Rituximab Re-Treatment
    Participants entering the Re-Treatment Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Re-Treatment Day 1 of the Substudy.

Primary Outcome Measure

Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death [ Time Frame: Baseline up to PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months) ]

Locations (5)

FacilityCityStateZIPSite coordinators
University of California San Diego Medical CenterLa JollaCalifornia92093-5354-
Henry Ford Health SystemDetroitMichigan48202-
Memorial Sloan Kettering Cancer Center; Clinical Trials OfficeNew YorkNew York10021-
Perlmutter Cancer Center NYU Langone HealthNew YorkNew York10032-
Huntsman Cancer Institute; University of UtahSalt Lake CityUtah84112-

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By condition
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By specialty
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By research site
University of California San Diego Medical Center· La Jolla, CAHenry Ford Health System· Detroit, MIMemorial Sloan Kettering Cancer Center; Clinical Trials Office· New York, NYPerlmutter Cancer Center NYU Langone Health· New York, NYHuntsman Cancer Institute; University of Utah· Salt Lake City, UT

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