Clinical trial NCT01414205: A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Week 32
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 4 years, 5 months
measure: Duration of Response
timeFrame: Up to 4 years, 5 months
measure: Number of Participants Surviving at End-of-Study
timeFrame: Up to 4 years, 5 months
measure: Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 4 years, 5 months
measure: Percentage of Participants With Adverse Events of Interest
timeFrame: Up to 4 years, 5 months
measure: Percentage of Participants With Adverse Events Leading to Study Discontinuation
timeFrame: Up to 4 years, 5 months
measure: PK Parameter: Maximum Serum Concentration (Cmax)
timeFrame: Day 148 (at end of infusion)
measure: PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )
timeFrame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
measure: PK Parameter: Clearance at Steady State (CLss)
timeFrame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
measure: PK Parameter: Volume of Distribution at Steady State (Vss)
timeFrame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
measure: PK Parameter: Terminal Half-Life (t1/2)
timeFrame: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
measure: PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits)
timeFrame: Months 3, 6, 9, and 12
measure: Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion
timeFrame: Up to 4 years, 5 months
measure: Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery
timeFrame: Up to 4 years, 5 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham; UAB Comprehensive Cancer Ctr
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Ctr
state: Arizona
city: La Jolla
country: United States
facility: University of California; Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Can Ctr; IDS Pharm
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Pasadena
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Aurora
country: United States
facility: Univ of Colorado Canc Ctr
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center; Medical Oncology
state: Colorado
city: Post Falls
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Goshen
country: United States
facility: Goshen Hlth Sys Ctr Can Care
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Paducah
country: United States
facility: Purchase Cancer Group
state: Kentucky
city: Morristown
country: United States
facility: Hem Onc Assoc of Northern NJ; Carol G. Simon Canc Ctr
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: Mark H. Zangmeister Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Cancer Inst of OK
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Ctr - 520 Country Club
state: Oregon
city: Dallas
country: United States
facility: Texas Oncology-Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian Hospital
state: Texas
city: Fort Worth
country: United States
facility: US Oncology Research Pharm.
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Roanoke
country: United States
facility: SW Virginia Hem Onc
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Byrd JC, Flynn JM, Kipps TJ, Boxer M, Kolibaba KS, Carlile DJ, Fingerle-Rowson G, Tyson N, Hirata J, Sharman JP. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood. 2016 Jan 7;127(1):79-86. doi: 10.1182/blood-2015-03-634394. Epub 2015 Oct 15.