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A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01414205
First Posted: August 11, 2011
Last Update Posted: April 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
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.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic Drug: Obinutuzumab Drug: Corticosteroids Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Randomized Phase II Trial Comparing the Efficacy, Safety, and Pharmacokinetics of GA101 1000 mg Versus 2000 mg in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Week 32 ]
    ORR was defined as the percentage of participants with complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR) as assessed by the investigator according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines two months after last treatment. CR required: blood lymphocytes < 4 x 10^9/Liter (L), absence of lymphadenopathy (≤ 1.5 centimeter (cm) in long axis by Computed Tomography), no hepatomegaly or splenomegaly, absence of disease, Neutrophils > 1.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin >11 g/dL, bone marrow normal and lymphoid nodules absent. CRi was CR with incomplete marrow recovery. PR required: 50% decrease in peripheral blood lymphocyte count, 50% reduction in lymphadenopathy, 50% reduction of liver and/or spleen enlargement if enlarged at baseline, Neutrophils > 1.5 x 10^9/L or > 50% of pretreatment value, Platelets > 100 x 10^9/L or 50% of pretreatment value and Hemoglobin > 11 g/dL or > 50% of pretreatment value.


Secondary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Up to 4 years, 5 months ]
    PFS was defined as the time from the randomization to the first occurrence of progression or death, whichever occurred first.

  • Duration of Response [ Time Frame: Up to 4 years, 5 months ]
  • Number of Participants Surviving at End-of-Study [ Time Frame: Up to 4 years, 5 months ]
  • Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to 4 years, 5 months ]
    An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator. Additional information about AEs can be found in the Adverse Event Section.

  • Percentage of Participants With Adverse Events of Interest [ Time Frame: Up to 4 years, 5 months ]
    Adverse Events of interest for this study were: serious infusion related reactions during or within 24 hours of infusion, serious neutropenia, serious infection, tumor lysis syndrome and Hepatitis B reactivation.

  • Percentage of Participants With Adverse Events Leading to Study Discontinuation [ Time Frame: Up to 4 years, 5 months ]
    An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

  • PK Parameter: Maximum Serum Concentration (Cmax) [ Time Frame: Day 148 (at end of infusion) ]
    Blood was collected for Pharmacokinetic (PK) Parameter Cmax after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

  • PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt ) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in day times micrograms per milliliter (day*μg/mL).

  • PK Parameter: Clearance at Steady State (CLss) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLss is reported in milliliters per day (mL/day).

  • PK Parameter: Volume of Distribution at Steady State (Vss) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss is reported in liters.

  • PK Parameter: Terminal Half-Life (t1/2) [ Time Frame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion) ]
    Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). T1/2 was reported in Days.

  • PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) [ Time Frame: Months 3, 6, 9, and 12 ]
    Blood serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

  • Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion [ Time Frame: Up to 4 years, 5 months ]
    Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell depletion was defined as a CD19 result < 0.07 × 10^9/L after at least one dose of study drug has been administered.

  • Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery [ Time Frame: Up to 4 years, 5 months ]
    Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as a CD19 result ≥ 0.07 × 10^9/L, where CD19 was previously depleted. B-cell recovery was only considered possible following the last dose of study treatment. The number of participants with B-cell recovery from End of Treatment to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) [PD before B-cell recovery or PD within 45 days after recovery] or Recovery without PD. PD required one of the following: 50% increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50% increase in the longest diameter of any previous site of lymphadenopathy, 50% increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.


Enrollment: 80
Actual Study Start Date: October 31, 2011
Study Completion Date: March 31, 2016
Primary Completion Date: March 31, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Obinutuzumab 1000 mg
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Drug: Obinutuzumab
Participants were administered obinutuzumab either at 1000 mg or 2000 mg on Day 1, 8, 15 of Cycle 1 and then on Day 1 of each 21 day cycles for up to 8 cycles.
Other Name: RO5072759; GA101
Drug: Corticosteroids
Participants were administered corticosteroids IV prior to the initial dose.
Experimental: Obinutuzumab 2000 mg
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Drug: Obinutuzumab
Participants were administered obinutuzumab either at 1000 mg or 2000 mg on Day 1, 8, 15 of Cycle 1 and then on Day 1 of each 21 day cycles for up to 8 cycles.
Other Name: RO5072759; GA101
Drug: Corticosteroids
Participants were administered corticosteroids IV prior to the initial dose.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01414205


  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham; UAB Comprehensive Cancer Ctr
Birmingham, Alabama, United States, 35291-3300
United States, Arizona
Arizona Oncology
Tucson, Arizona, United States, 85704
Arizona Clinical Research Ctr
Tucson, Arizona, United States, 85715
United States, California
University of California; Moores Cancer Center
La Jolla, California, United States, 92093
USC Norris Cancer Center
Los Angeles, California, United States, 90033
USC/Norris Can Ctr; IDS Pharm
Los Angeles, California, United States, 90033
Ventura County Hematology-Oncology Specialists
Oxnard, California, United States, 93030
Wilshire Oncology Medical Group
Pasadena, California, United States, 91750
United States, Colorado
Univ of Colorado Canc Ctr
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Center; Medical Oncology
Denver, Colorado, United States, 80218
United States, Idaho
Kootenai Cancer Center
Post Falls, Idaho, United States, 83854
United States, Indiana
Goshen Hlth Sys Ctr Can Care
Goshen, Indiana, United States, 46526
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States, 47905
United States, Kentucky
Purchase Cancer Group
Paducah, Kentucky, United States, 42001
United States, New Jersey
Hem Onc Assoc of Northern NJ; Carol G. Simon Canc Ctr
Morristown, New Jersey, United States, 07962
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Mark H. Zangmeister Center
Columbus, Ohio, United States, 43219
Kettering Medical Center
Kettering, Ohio, United States, 45429
United States, Oklahoma
INTEGRIS Cancer Inst of OK
Oklahoma City, Oklahoma, United States, 73142
United States, Oregon
Willamette Valley Cancer Ctr - 520 Country Club
Eugene, Oregon, United States, 97401-8122
United States, Texas
Texas Oncology-Medical City Dallas
Dallas, Texas, United States, 75230
Texas Oncology - Dallas Presbyterian Hospital
Dallas, Texas, United States, 75231
US Oncology Research Pharm.
Fort Worth, Texas, United States, 76177
Texas Cancer Center - Sherman
Sherman, Texas, United States, 75090-0504
United States, Virginia
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States, 22031
SW Virginia Hem Onc
Roanoke, Virginia, United States, 24014
Shenandoah Oncology Associates
Winchester, Virginia, United States, 22601
United States, Washington
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, United States, 98684
Yakima Valley Memorial Hospital/North Star Lodge
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01414205     History of Changes
Other Study ID Numbers: GAO4768g
GO25677 ( Other Identifier: Hoffmann-La Roche )
First Submitted: August 10, 2011
First Posted: August 11, 2011
Results First Submitted: March 21, 2014
Results First Posted: April 24, 2014
Last Update Posted: April 17, 2017
Last Verified: March 2017

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
Obinutuzumab
Antineoplastic Agents