A Study of Obinutuzumab [RO5072759 (GA101)] in Combination With CHOP Chemotherapy in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma (GATHER)

NCT01414855 | Completed Phase 2 Results DMC

• 1 other identifier: GAO4915g
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 38

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.

Conditions

Lymphoma, B-Cell

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment

  Complete response rate is defined as the percentage of participants with Complete Response (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT). CR is the disappearance of all evidence of disease.

  From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

• Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment

  Overall response rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, FDG-PET and computed tomography (CT). CR is the disappearance of all evidence of disease. PR is at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.

  From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Secondary Outcomes (12)

• Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment

  From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

• Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment

  From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

• Progression-Free Survival (PFS) as Assessed by the Investigator

  From the first dose of study treatment to PFS assessment (up to 64 months)

• Duration of Response (DOR)

  From the response assessment to relapse, progression, or death (up to 64 months)

• Percentage of Participants With Adverse Events as a Measure of Safety

  From the first dose of study treatment to end of study (up to 5 years 4 months)

Study Arms (1)

obinutuzumab + CHOP

EXPERIMENTAL

Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles.

Drug: obinutuzumab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: prednisone; Drug: vincristine

Interventions

obinutuzumab DRUG

1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15.

obinutuzumab + CHOP

cyclophosphamide DRUG

750 mg/m\^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles.

obinutuzumab + CHOP

doxorubicin DRUG

50 mg/m\^2 IV, Day 1 of each 21-cycle, 6 cycles.

obinutuzumab + CHOP

prednisone DRUG

100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles.

obinutuzumab + CHOP

vincristine DRUG

1.4 mg/m\^2 IV, Day 1 of each 21-day cycle, 6 cycles.

obinutuzumab + CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (38)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

Location

cCare

Encinitas, California, 92024, United States

Location

University of Colorado Cancer Center Department of Hematology

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Ctr - Denver (Williams)

Denver, Colorado, 80218, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Florida Cancer Specialists; Department of Oncology

Fort Myers, Florida, 33901-8101, United States

Location

Florida Cancer Specialists; Saint Petersburg

St. Petersburg, Florida, 33719, United States

Location

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

Kootenai Medical Center

Coeur d'Alene, Idaho, 83814, United States

Location

Northwestern University; Robert H. Lurie Comp Can Ctr

Chicago, Illinois, 60611, United States

Location

Onc Hem Assoc of Central IL

Peoria, Illinois, 61615-7828, United States

Location

McFarland Clinic

Ames, Iowa, 50010, United States

Location

Jewish Cancer Care

Louisville, Kentucky, 40245, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0934, United States

Location

MT Cancer Inst Fndtn; MT Can Spec

Missoula, Montana, 59802, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

MSKCC at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Memorial Sloan-Kettering; Cancer Center

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MSKCC at Mercy Med Ctr

Rockville Centre, New York, 11570, United States

Location

MSKCC at Sleepy Hollow

Sleepy Hollow, New York, 10591, United States

Location

Emerywood Hematology and Onc

High Point, North Carolina, 27262, United States

Location

Willamette Valley Cancer Insitute and Research Center

Springfield, Oregon, 97477, United States

Location

Medical University of SC (MUSC)

Charleston, South Carolina, 29425, United States

Location

SCRI-Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Onc & Hem Assoc; USO Cent Pharm

Fort Worth, Texas, 76177, United States

Location

MD Anderson Cancer Center Department of Lymphoma & Myeloma

Houston, Texas, 77030, United States

Location

Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

Cancer Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

USO - Tyler Cancer Ctr

Tyler, Texas, 75702, United States

Location

Blue Ridge Cancer Care - Roanoke

Roanoke, Virginia, 24014, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208, United States

Location

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, 98684, United States

Location

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, 98902, United States

Location

Aurora Bay Care Medical Center

Green Bay, Wisconsin, 54311, United States

Location

Related Publications (2)

• 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.

  PMID: 31050355 DERIVED

• 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.

  PMID: 30277102 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

obinutuzumab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

genetech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: August 11, 2011
• Study Start: August 31, 2011
• Primary Completion: December 31, 2013
• Study Completion: December 23, 2016
• Last Updated: April 25, 2018
• Results First Posted: March 19, 2015

Record last verified: 2018-04

Locations

US (38)