A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)

NCT ID: NCT01300247

Last Updated: 2017-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-12-31

Brief 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.

Conditions

Lymphocytic Leukemia, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Obinutuzumab + Fludarabine + Cyclophosphamide

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), 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), and 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).

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Obinutuzumab

Intervention Type: DRUG

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Obinutuzumab + Bendamustine

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.

Bendamustine

Intervention Type: DRUG

Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.

Interventions

Fludarabine

Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Intervention Type: DRUG

Obinutuzumab

Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.

Intervention Type: DRUG

Bendamustine

Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.

Intervention Type: DRUG

Cyclophosphamide

Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Intervention Type: DRUG

Other Intervention Names

RO5072759; GA101

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 (<=) 60 milliliters per minute (mL/min), calculated according to the formula of Cockcroft and Gault
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Huntsville, Alabama, United States

Duarte, California, United States

La Jolla, California, United States

Los Angeles, California, United States

Southington, Connecticut, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Marietta, Georgia, United States

Chicago, Illinois, United States

Boston, Maryland, United States

Boston, Massachusetts, United States

Saint Louis Park, Minnesota, United States

Springfield, Missouri, United States

Rochester, New York, United States

Houston, Texas, United States

Seattle, Washington, United States

Tacoma, Washington, United States

Madison, Wisconsin, United States

Countries

United States

References

Brown JR, O'Brien S, Kingsley CD, Eradat H, Pagel JM, Lymp J, Hirata J, Kipps TJ. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood. 2015 Apr 30;125(18):2779-85. doi: 10.1182/blood-2014-12-613570. Epub 2015 Mar 13.

Reference Type: DERIVED

PMID: 25769620 (View on PubMed)

Other Identifiers

GO01298

Identifier Type: OTHER

Identifier Source: secondary_id

GAO4779g

Identifier Type: -

Identifier Source: org_study_id