Clinical trial NCT01414855: A Study of Obinutuzumab [RO5072759 (GA101)] in Combination With CHOP Chemotherapy in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma (GATHER)
Official title: A Phase II, Open-Label, Multicenter Study of Efficacy, Safety, and Biomarkers in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma Treated With GA101 (RO5072759) in Combination With CHOP Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, B-Cell
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, multicenter study will evaluate the efficacy and safety of obinutuzumab \[RO5072759 (GA101)\] in combination with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) chemotherapy in patients with advanced diffuse large B-cell lymphoma. Patients will receive 8 cycles of obinutuzumab (1000 mg intravenously on Day 1 of each 21-day cycle, during Cycle 1 obinutuzumab will also be infused on Days 8 and 15) in combination with CHOP chemotherapy on Day 1 of cycles 1 to 6. A substudy will investigate the drug-drug interaction of obinutuzumab with CHOP chemotherapy agents. For the substudy, an additional cohort of approximately 15 patients are planned to be enrolled at a subset of investigational sites.


Eligibility criteria: Inclusion Criteria:

* Adult patients, ≥18 years of age
* Previously untreated cluster of differentiation antigen 20 (CD20)-positive diffuse large B-cell lymphoma
* Ann Arbour Stage III/IV and bulky II (mass \>10 cm)
* At least one bi-dimensionally measurable lesion defined as \>1.5 cm in its largest dimension by CT scan
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Left ventricular ejection fraction ≥50%
* Adequate hematologic function

Exclusion Criteria:

* Transformed lymphoma (follicular IIIB) if previously treated with chemotherapy or immunotherapy
* Prior therapy for diffuse large B-cell lymphoma except for nodal biopsy or local irradiation
* Central nervous system (CNS) lymphoma, primary mediastinal large cell lymphoma, primary cutaneous lymphoma, primary effusion lymphoma
* Patients who received cytotoxic drugs or rituximab as part of their treatment for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody
* Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
* Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
* History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix, or malignancy treated with or without curative intent and in remission without treatment for ≥2 years prior to enrolment
* Positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV-1) infection
* Pregnant or lactating women

Primary outcomes:
measure: Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment
timeFrame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
measure: Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment
timeFrame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Secondary outcomes:
measure: Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment
timeFrame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
measure: Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment
timeFrame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
measure: Progression-Free Survival (PFS) as Assessed by the Investigator
timeFrame: From the first dose of study treatment to PFS assessment (up to 64 months)
measure: Duration of Response (DOR)
timeFrame: From the response assessment to relapse, progression, or death (up to 64 months)
measure: Percentage of Participants With Adverse Events as a Measure of Safety
timeFrame: From the first dose of study treatment to end of study (up to 5 years 4 months)
measure: Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI)
timeFrame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
measure: Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab
timeFrame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
measure: Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab
timeFrame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
measure: Pharmacokinetics: Clearance (Cl) for Obinutuzumab
timeFrame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
measure: Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab
timeFrame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
measure: Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day)
timeFrame: Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12
measure: Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Encinitas
country: United States
facility: cCare
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center Department of Hematology
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Ctr - Denver (Williams)
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists; Department of Oncology
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists; Saint Petersburg
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Medical Center
state: Idaho
city: Chicago
country: United States
facility: Northwestern University; Robert H. Lurie Comp Can Ctr
state: Illinois
city: Peoria
country: United States
facility: Onc Hem Assoc of Central IL
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Louisville
country: United States
facility: Jewish Cancer Care
state: Kentucky
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Missoula
country: United States
facility: MT Cancer Inst Fndtn; MT Can Spec
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Basking Ridge
country: United States
facility: MSKCC at Basking Ridge
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Commack
country: United States
facility: Memorial Sloan-Kettering; Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: MSKCC at Mercy Med Ctr
state: New York
city: Sleepy Hollow
country: United States
facility: MSKCC at Sleepy Hollow
state: New York
city: High Point
country: United States
facility: Emerywood Hematology and Onc
state: North Carolina
city: Springfield
country: United States
facility: Willamette Valley Cancer Insitute and Research Center
state: Oregon
city: Charleston
country: United States
facility: Medical University of SC (MUSC)
state: South Carolina
city: Nashville
country: United States
facility: SCRI-Tennessee Oncology
state: Tennessee
city: Fort Worth
country: United States
facility: Onc & Hem Assoc; USO Cent Pharm
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center Department of Lymphoma & Myeloma
state: Texas
city: Houston
country: United States
facility: Methodist Hospital Research Institute
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center
state: Texas
city: Tyler
country: United States
facility: USO - Tyler Cancer Ctr
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care - Roanoke
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
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
city: Green Bay
country: United States
facility: Aurora Bay Care Medical Center
state: Wisconsin
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
citation: Sharman JP, Forero-Torres A, Costa LJ, Flinn IW, Inhorn L, Kelly K, Bessudo A, Fayad LE, Kaminski MS, Evens AM, Flowers CR, Sahin D, Mundt KE, Sandmann T, Fingerle-Rowson G, Vignal C, Mobasher M, Zelenetz AD. Obinutuzumab plus CHOP is effective and has a tolerable safety profile in previously untreated, advanced diffuse large B-cell lymphoma: the phase II GATHER study. Leuk Lymphoma. 2019 Apr;60(4):894-903. doi: 10.1080/10428194.2018.1515940. Epub 2018 Oct 2.