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 (</=) 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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in November 2016.