Phase 2
Completed N=80
A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)
Lymphocytic Leukemia, Chronic
Source: ClinicalTrials.gov NCT01414205 ↗
Enrolled (actual)
80
Serious AEs
20.5%
Results posted
Apr 2014
Primary outcomePrimary: Objective Response Rate (ORR) — 48.8; 66.7 Percentage of participants — p=0.0779
Summary
This open-label, multicenter, randomized study compared the efficacy, safety and pharmacokinetics of obinutuzumab (RO5072759; GA101) 1000 mg versus 2000 mg in participants with previously untreated CLL. Participants were randomized to receive a maximum of 8 cycles (28-day cycle) of obinutuzumab (1000 mg intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles or maximum of 8 cycles of obinutuzumab (2000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of each subsequent cycle up to 8 cycles.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (ORR) |
48.8; 66.7 | 0.0779 |
| SECONDARY Progression-free Survival (PFS) |
25.2; 26.0 | — |
| SECONDARY Duration of Response |
— | — |
| SECONDARY Number of Participants Surviving at End-of-Study |
35; 37 | — |
| SECONDARY Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
100.0; 100.0; 20.0; 21.1 | — |
| SECONDARY Percentage of Participants With Adverse Events of Interest |
7.5; 5.3; 5.0; 5.3; 5.0; 5.3 | — |
| SECONDARY Percentage of Participants With Adverse Events Leading to Study Discontinuation |
0; 0 | — |
| SECONDARY PK Parameter: Maximum Serum Concentration (Cmax) |
600; 1190 | — |
| SECONDARY PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt ) |
8230; 16500 | — |
| SECONDARY PK Parameter: Clearance at Steady State (CLss) |
121; 122 | — |
| SECONDARY PK Parameter: Volume of Distribution at Steady State (Vss) |
7.08; 6.68 | — |
| SECONDARY PK Parameter: Terminal Half-Life (t1/2) |
30.6; 26.3 | — |
| SECONDARY PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) |
41.2; 98.9; 15; 12.6; 2.63; 4.09 | — |
| SECONDARY Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion |
31; 31; 28; 28; 16; 17 | — |
| SECONDARY Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery |
0; 0; 2; 3; 1; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed diagnosis of CD20-positive B-cell CLL (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
- Confirmed diagnosis of 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 hepatitis B surface antigen [HBsAg] serology)
- Positive for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
- Pregnant or lactating women
- Concurrent (or within 7 days prior to first dose of study treatment) systemic corticosteroid use, except for low-dose corticosteroid therapy used to treat chronic medical conditions
Data sourced from ClinicalTrials.gov (NCT01414205). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.