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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01300247
First received: February 14, 2011
Last updated: May 18, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Drug: Fludarabine
Drug: Obinutuzumab
Drug: Bendamustine
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase Ib Trial of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Number of Participants With Human Anti-Human Antibodies (HAHAs) [ Time Frame: Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Maximum Plasma Concentration (Cmax) of Obinutuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Trough Plasma Concentration (Ctrough) of Obinutuzumab [ Time Frame: Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1 ] [ Designated as safety issue: No ]
  • Clearance of Obinutuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Volume of Distribution of Obinutuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  • Half-Life of Obinutuzumab [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Objective response was defined as a complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR), as determined by investigator. CR:required peripheral blood lymphocytes <4x10^9/L; absence of lymphadenopathy; no hepatomegaly or splenomegaly by physical examination as determined by measurement below relevant costal margin; absence of disease/constitutional symptoms; bone marrow at least normocellular for age, with <30% of nucleated cells being lymphocytes. PR:Greater than equal to (>=) 50% decrease in peripheral blood lymphocyte count, >=50% reduction in lymphadenopathy, >=50% reduction of liver and/or spleen enlargement, either neutrophil, platelet, or hemoglobin (Hb) recovery. CRi:met all CR criteria including confirmed lymphocyte infiltration <30%; may not meet Hb, platelet or neutrophil count recovery. The 95% confidence interval (CI) was estimated by Clopper-Pearson method. The end of treatment response visit occurred 2-3 months after end of treatment.

  • Duration of Objective Response, Assessed by the Investigator According to IWCLL Guidelines [ Time Frame: From first documented objective response up to disease progression or relapse or death, whichever occurred first (up to approximately 3.75 years) ] [ Designated as safety issue: No ]
    Duration of response (DOR) was defined, among participants with an objective response, as the time from documentation of the first CR, CRi or PR to the time of disease progression, relapse, or death from any cause, as assessed by the investigator. Please refer Outcome Measure 8 for the definition of CR CRi and PR. Disease progression: >=50% increase in the absolute number of circulating lymphocytes to at least 5x10^9/L; Appearance of new palpable lymph nodes (>15 millimeters [mm] in longest diameter) or any new extra-nodal lesion; >=50% increase in the longest diameter of any previous site of lymphadenopathy; >=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology.

  • Percentage of Participants Who Were Alive and Progression Free [ Time Frame: Baseline up to relapse or progression or death from any cause, whichever occurred first up to end of treatment response visit (up to 6 months) ] [ Designated as safety issue: No ]
    Progressive disease assessed using IWCLL: >=50% increase in the absolute number of circulating lymphocytes to at least 5x10^9/L; Appearance of new palpable lymph nodes (>15 millimeters [mm] in longest diameter) or any new extra-nodal lesion; >=50% increase in the longest diameter of any previous site of lymphadenopathy; >=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology. The 95% confidence interval (CI) was estimated by Clopper-Pearson method.

  • Percentage of Participants Who Were Alive [ Time Frame: Baseline up to relapse or progression or death from any cause, whichever occurred first up to end of treatment response visit (up to 6 months) ] [ Designated as safety issue: No ]
    The 95% CI was estimated by Clopper-Pearson method.

  • Percentage of Participants Who Had B-Cell Depletion [ Time Frame: Up to the end of the treatment period, and follow-up at 6 months, 6-12 months and after 12 months up to data cutoff date 24 January 2013 (up to approximately 1.75 years) ] [ Designated as safety issue: No ]
    B-cell depletion was defined as cluster of differentiation 19 (CD19) <0.07×10^9/L and could occur only after at least one dose of study drug had been administered.

  • Percentage of Participants Who Had B-Cell Recovery [ Time Frame: Follow-up at 6 months, 6-12 months and after 12 months up to data cutoff date 24 January 2013 (up to approximately 1.75 years) ] [ Designated as safety issue: No ]
    B-cell recovery was defined as CD19 >=0.07×10^9/L, where participants' CD19 were previously depleted. B-cell recovery was only considered possible when the participant had received the last dose of study treatment.


Enrollment: 41
Study Start Date: May 2011
Study Completion Date: December 2015
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: 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.
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.
Other Name: RO5072759; GA101
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.
Experimental: 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).
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.
Other Name: RO5072759; GA101
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01300247

Locations
United States, Alabama
Huntsville, Alabama, United States, 35805
United States, California
Duarte, California, United States, 91010
La Jolla, California, United States, 92093
Los Angeles, California, United States, 90095
United States, Connecticut
Southington, Connecticut, United States, 06489
United States, Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Atlanta, Georgia, United States, 30322
Marietta, Georgia, United States, 30060
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Maryland
Boston, Maryland, United States, 02115
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Minnesota
St. Louis Park, Minnesota, United States, 55426
United States, Missouri
Springfield, Missouri, United States, 65807
United States, New York
Rochester, New York, United States, 14642
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98109
Tacoma, Washington, United States, 98405
United States, Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01300247     History of Changes
Other Study ID Numbers: GAO4779g  GO01298 
Study First Received: February 14, 2011
Results First Received: May 18, 2016
Last Updated: May 18, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Bendamustine Hydrochloride
Fludarabine
Obinutuzumab
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 07, 2016