Overview

This trial is active, not recruiting.

Condition lymphocytic leukemia, chronic
Treatment obinutuzumab
Phase phase 2
Target CD20
Sponsor Genentech
Start date October 2011
End date March 2013
Trial size 80 participants
Trial identifier NCT01414205, GAO4768g, GO25677

Summary

This open-label, multicenter, randomized study will compare the efficacy, safety and pharmacokinetics of RO5072759 (GA101) 1000 mg versus 2000 mg in patients with previously untreated chronic lymphocytic leukemia. The randomization scheme will ensure approximately equal sample sizes in the two treatment dose arms for the following stratification factors: 1) tumor burden at baseline (high or low); and 2) Rai stage at baseline (study entry; I/II or III/IV). Tumor burden will be assessed on the basis of the presence or absence of at least one nodal mass >/= 5 cm in the baseline computed tomography (CT) scan. Patients will be randomized to receive a maximum of 8 cycles of GA101: 1000mg intravenous (iv) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8 on 21 day cycles or maximum of 8 cycles of GA101 2000mg iv infusion, on days 1 (split dose 100 mg on Day 1, 900 mg on Day 2, 1000 mg on Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8 on 21 day cycles.

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)
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
obinutuzumab RO5072759
Obinutuzumab (RO5072759) Repeating intravenous dose.
(Experimental)
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
obinutuzumab RO5072759
Obinutuzumab (RO5072759) Repeating intravenous dose.

Primary Outcomes

Measure
Objective Response Rate (ORR)
time frame: Week 32

Secondary Outcomes

Measure
Progression-free Survival (PFS)
time frame: up to 3.5 years
Duration of Response
time frame: up to 3.5 years
Overall Survival (OS)
time frame: up to 3.5 years
Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
time frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years)
Percentage of Participants With Adverse Events of Interest
time frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years)
Percentage of Participants With Adverse Events Leading to Study Discontinuation
time frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years)
PK Parameter: Maximum Serum Concentration (Cmax)
time frame: Day 148 (at end of infusion)
PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )
time frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
PK Parameter: Clearance at Steady State (CLss)
time frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
PK Parameter: Volume of Distribution at Steady State (Vss)
time frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
PK Parameter: Terminal Half-Life (t1/2)
time frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion
time frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years)
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery
time frame: Randomization to Clinical data cut-off: 27 April 2013 (Up to 1.5 years)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Cluster of differentiation antigen 20 (CD20)-positive B-cell chronic lymphocytic leukemia [per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines] - Rai Stage III/IV or Binet Stage C disease, or Rai Stage I/II or Binet Stage B disease that requires treatment according to IWCLL guidelines - No previous treatment for CLL chemotherapy, radiotherapy or immunotherapy; no previous rituximab treatment for autoimmune hemolytic anemia (AIHA) or Idiopathic thrombocytopenic purpura (ITP); prior use of steroids for AIHA or ITP is allowed - Eastern Cooperative Oncology Group performance status of 0, 1 or 2 Exclusion Criteria: - Transformation of CLL to aggressive B-cell malignancy - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy - Evidence of severe, uncontrolled concomitant disease - Known active infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks before the start of Cycle 1 - Seropositive for human immunodeficiency virus (HIV) - Positive for chronic hepatitis B infection (defined as positive HBsAg serology) - Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing) - Pregnant or lactating women - Concurrent (or within 7 days prior to fist dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat illness other than lymphoma

Additional Information

Official title An Open-label, Multicenter, Randomized Phase II Trial Comparing the Efficacy, Safety, and Pharmacokinetics of GA101 1000 mg Versus 2000 mg in Patients With Previously Untreated Chronic Lymphocytic Leukemia
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Genentech.