Overview

This trial is active, not recruiting.

Condition lymphoma, b-cell
Treatments obinutuzumab, cyclophosphamide, doxorubicin, prednisone, vincristine
Phase phase 2
Target CD20
Sponsor Genentech, Inc.
Start date August 2011
End date December 2013
Trial size 100 participants
Trial identifier NCT01414855, GAO4915g

Summary

This open-label, multicenter study will evaluate the efficacy and safety of obinutuzumab [RO5072759 (GA101)] in combination with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) chemotherapy in patients with advanced diffuse large B-cell lymphoma. Patients will receive 8 cycles of obinutuzumab (1000 mg intravenously on Day 1 of each 21-day cycle, during Cycle 1 obinutuzumab will also be infused on Days 8 and 15) in combination with CHOP chemotherapy on Day 1 of cycles 1 to 6. A substudy will investigate the drug-drug interaction of obinutuzumab with CHOP chemotherapy agents. For the substudy, an additional cohort of approximately 15 patients are planned to be enrolled at a subset of investigational sites.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.
obinutuzumab
1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15.
cyclophosphamide
750 mg/m^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles.
doxorubicin
50 mg/m^2 IV, Day 1 of each 21-cycle, 6 cycles.
prednisone
100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles.
vincristine
1.4 mg/m^2 IV, Day 1 of each 21-day cycle, 6 cycles.

Primary Outcomes

Measure
Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Secondary Outcomes

Measure
Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Progression-Free Survival (PFS) as Assessed by the Investigator
time frame: From the first dose of study treatment to PFS assessment (Up to 28 months)
Duration of Response (DOR)
time frame: From the first dose of study treatment to response assessment (Up to 28 months)
Percentage of Participants With Adverse Events as a Measure of Safety
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI)
time frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab
time frame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab
time frame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
Pharmacokinetics: Clearance (Cl) for Obinutuzumab
time frame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab
time frame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day)
time frame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count
time frame: Up to approximately 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients, ≥18 years of age - Previously untreated cluster of differentiation antigen 20 (CD20)-positive diffuse large B-cell lymphoma - Ann Arbour Stage III/IV and bulky II (mass >10 cm) - At least one bi-dimensionally measurable lesion defined as >1.5 cm in its largest dimension by CT scan - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Left ventricular ejection fraction ≥50% - Adequate hematologic function Exclusion Criteria: - Transformed lymphoma (follicular IIIB) if previously treated with chemotherapy or immunotherapy - Prior therapy for diffuse large B-cell lymphoma except for nodal biopsy or local irradiation - Central nervous system (CNS) lymphoma, primary mediastinal large cell lymphoma, primary cutaneous lymphoma, primary effusion lymphoma - Patients who received cytotoxic drugs or rituximab as part of their treatment for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody - Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1 - Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy - History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix, or malignancy treated with or without curative intent and in remission without treatment for ≥2 years prior to enrolment - Positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV-1) infection - Pregnant or lactating women

Additional Information

Official title A Phase II, Open-Label, Multicenter Study of Efficacy, Safety, and Biomarkers in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma Treated With GA101 (RO5072759) in Combination With CHOP Chemotherapy
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Genentech, Inc..