Clinical trial NCT01300247: A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)
Official title: An Open-Label, Multicenter, Phase Ib Trial of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Human Anti-Human Antibodies (HAHAs)
timeFrame: Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years)
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab
timeFrame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
measure: Maximum Plasma Concentration (Cmax) of Obinutuzumab
timeFrame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
measure: Trough Plasma Concentration (Ctrough) of Obinutuzumab
timeFrame: Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1
measure: Clearance of Obinutuzumab
timeFrame: Pre-dose on C1D1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
measure: Volume of Distribution of Obinutuzumab
timeFrame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
measure: Half-Life of Obinutuzumab
timeFrame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
measure: Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
timeFrame: Baseline up to relapse or progression or death from any cause, whichever occurred first up to end of treatment response visit (up to approximately 9 months)
measure: Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines
timeFrame: From first documented objective response up to disease progression or relapse or death, whichever occurred first (up to approximately 6 months)
measure: Percentage of Participants Who Were Alive and Progression Free
timeFrame: Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)
measure: Percentage of Participants Who Were Alive
timeFrame: Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)
measure: Percentage of Participants Who Had B-Cell Depletion
timeFrame: Up to the end of the treatment period, and follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)
measure: Percentage of Participants Who Had B-Cell Recovery
timeFrame: Follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Duarte
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Southington
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: St. Louis Park
country: United States
state: Minnesota
city: Springfield
country: United States
state: Missouri
city: Rochester
country: United States
state: New York
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.