Phase 1
Completed N=41
A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)
Lymphocytic Leukemia, Chronic
Source: ClinicalTrials.gov NCT01300247 ↗
Enrolled (actual)
41
Serious AEs
41.5%
Results posted
Jun 2016
Primary outcomePrimary: Number of Participants With Human Anti-Human Antibodies (HAHAs) — 0; 0 participants
Summary
This open-label, 2-arm, nonrandomized, multicenter, Phase Ib study will investigate the safety and efficacy of obinutuzumab (RO5072759; GA101) administered in combination with chemotherapy (bendamustine or fludarabine + cyclophosphamide [FC] regimens) in participants with previously untreated cluster of differentiation 20 (CD20)-positive B-CLL. Participants will be enrolled to receive a maximum of 6 cycles of obinutuzumab (1000 milligrams [mg] intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus bendamustine (90 milligrams per meter square [mg/m^2] IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2 - 6) on 28 day cycles or a maximum of 6 cycles of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus FC (fludarabine 25 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2 - 6; cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2 - 6) on 28 day cycles.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Human Anti-Human Antibodies (HAHAs) |
0; 0 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab |
— | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Obinutuzumab |
— | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Obinutuzumab |
— | — |
| SECONDARY Clearance of Obinutuzumab |
— | — |
| SECONDARY Volume of Distribution of Obinutuzumab |
— | — |
| SECONDARY Half-Life of Obinutuzumab |
— | — |
| SECONDARY Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines |
61.9; 90.0 | — |
| SECONDARY Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines |
NA; 100.00 | — |
| SECONDARY Percentage of Participants Who Were Alive and Progression Free |
90.5; 90.0 | — |
| SECONDARY Percentage of Participants Who Were Alive |
95.2; 95.0 | — |
| SECONDARY Percentage of Participants Who Had B-Cell Depletion |
90.5; 100.0; 85.7; 100.0; 81.0; 100.0 | — |
| SECONDARY Percentage of Participants Who Had B-Cell Recovery |
0; 0; 9.5; 0; 42.9; 30.0 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed diagnosis of CD20-positive B-CLL
- Rai Stage III/IV or Binet Stage C disease
- Rai Stage I/II or Binet Stage B disease that requires treatment
- Adequate baseline bone marrow function, unless there is clear evidence of extensive bone marrow involvement with tumor infiltration, myelodysplasia, or hypocellularity
- No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Life expectancy of greater than (>) 6 months
Exclusion Criteria
- Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1
- Transformation of CLL to aggressive B-cell malignancy
- Creatinine clearance less than equal to ( 2.5 times the upper limit of normal (ULN)
- Total bilirubin greater than equal to (>=) 3 x ULN
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- History of sensitivity to mannitol (if bendamustine is to be administered)
- 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, including significant cardiovascular disease or pulmonary disease
- Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1
- Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
- Known infection with human immunodeficiency virus (HIV) seropositive status
- Presence of positive test results for hepatitis B (hepatitis B virus [HBV] surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody serology testing). Participants with chronic HBV infection, occult HBV infection, or past HBV infection will be excluded. Participants who have received IV immunoglobulin within 3 months of enrollment and who are anti-HBc positive but HBV deoxyribonucleic acid (DNA) negative will be considered for inclusion on the study by the Medical Monitor on a case-by-case basis. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
- Women who are pregnant or lactating
- Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly
- Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid use except low-dose corticosteroid therapy used to treat an illness other than lymphoma
Data sourced from ClinicalTrials.gov (NCT01300247). 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.