Overview

This trial is active, not recruiting.

Condition follicular lymphoma
Treatments bendamustine, gdc-0199, rituximab
Phase phase 2
Targets BCL-2, CD20
Sponsor Hoffmann-La Roche
Collaborator AbbVie
Start date December 2014
End date March 2018
Trial size 165 participants
Trial identifier NCT02187861, 2014-000576-26, BO29337

Summary

This open-label, international, multicenter study will investigate the safety and efficacy of GDC-0199 in combination with bendamustine plus rituximab (GDC-0199 + 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 GDC-0199 in combination with rituximab (GDC-0199 + 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 GDC-0199 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. The anticipated time on study treatment is approximately 24-52 weeks, depending on treatment arm.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Safety run-in period: participants will receive GDC-0199 tablets (no more than 600 mg) orally once daily continuously along with rituximab (administered on Day 1 of 28-day cycle) and bendamustine (administered on Days 1 and 2 of the 28-day cycle). Safety run-in will continue until at least 6 participants have completed the safety observation window of 28 days.\nRandomization period: Participants will receive GDC-0199 tablets (at doses decided from safety run-in) orally once daily continuously for 1 year along with rituximab (administered on Day 1 of each 28-day cycle) and bendamustine (administered on Days 1 and 2 of each 28-day cycle), for 6 cycles.
bendamustine
Bendamustine will be administered as intravenous infusion at a dose of 90 milligrams per square meter (mg/m^2).
gdc-0199 ABT-199; RO5537382
GDC-0199 tablets will be administered orally once daily.
rituximab MabThera; Rituxan
Rituximab intravenous infusion will be administered at a dose of 375 mg/m^2.
(Active Comparator)
Participants will receive rituximab (administered on Day 1 of each 28-day cycle) and bendamustine (administered on Days 1 and 2 of each 28-day cycle), for 6 cycles.
bendamustine
Bendamustine will be administered as intravenous infusion at a dose of 90 milligrams per square meter (mg/m^2).
rituximab MabThera; Rituxan
Rituximab intravenous infusion will be administered at a dose of 375 mg/m^2.
(Experimental)
Participants will receive GDC-0199 800 mg tablets orally once daily for 1 year along with rituximab IV infusion once weekly for initial 4 doses (on Cycle 1 Days 1, 8, 15, 22) followed by every 8 weeks for 5 additional doses (on Day 1 of Cycles 4, 6, 8, 10, 12). Each cycle will be of 28 days.
gdc-0199 ABT-199; RO5537382
GDC-0199 tablets will be administered orally once daily.
rituximab MabThera; Rituxan
Rituximab intravenous infusion will be administered at a dose of 375 mg/m^2.

Primary Outcomes

Measure
Percentage of Participants With Complete Response, According to Independent Review Committee (IRC), As per Lugano Classification With the use of Positron Emission Tomography (PET) Scanning
time frame: 6-8 weeks after Cycle 6 Day 1 (Cycle length = 28 days)

Secondary Outcomes

Measure
Percentage of Participants With Complete Response, According to Investigator, As per Lugano Classification With the use of PET Scanning
time frame: 6-8 weeks after Cycle 6 Day 1 (Cycle length = 28 days)
Percentage of Participants With Complete Response, According to Investigator, As per Lugano Classification With the use of PET Scanning at Year 1
time frame: Year 1
Percentage of Participants With Complete Response, According to IRC, As per Lugano Classification With the use of Computed tomography (CT) Scanning
time frame: 6−8 weeks after Cycle 6 Day 1 (Cycle length = 28 days)
Percentage of Participants With Complete Response, According to Investigator, As per Lugano Classification With the use of CT Scan
time frame: 6−8 weeks after Cycle 6 Day 1 (Cycle length = 28 days), Year 1
Percentage of Participants With Objective Response, As per Lugano Classification With the use of PET Scanning
time frame: Baseline up to 40 months
Duration of Response, As per Lugano Classification With the use of PET ScanningB
time frame: Baseline up to 40 months
Progression-Free Survival, As per Lugano Classification
time frame: Baseline up to 40 months
Event-Free Survival, As per Lugano Classification
time frame: Baseline up to 40 months
Apparent Clearance of GDC-0199
time frame: Pre-dose (Hour 0) and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; Pre-dose (Hour 0) on Cycle 1 Days 8, 15, 22; pre-dose (Hour 0) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Apparent Volume of Distribution of GDC-0199
time frame: Pre-dose (Hour 0) and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; Pre-dose (Hour 0) on Cycle 1 Days 8, 15, 22; pre-dose (Hour 0) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)
Overall Survival
time frame: Baseline up to 40 months
Number of Participants With Adverse Events
time frame: Baseline up to 40 months

Eligibility Criteria

Male or female participants at least 18 years old.

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 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 GDC-0199 and 12 months after the last dose of rituximab, whichever is longer measures - 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 (

Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.