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

Lymphoma, B-Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01414855
• Other study ID #: GAO4915g
• Status: Completed
• Phase: Phase 2
• First received: August 10, 2011
• Last updated: April 24, 2018
• Start date: August 31, 2011
• Est. completion date: December 23, 2016

Study information

• Verified date: April 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 23, 2016
• Est. primary completion date: December 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• obinutuzumab
1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15.
• cyclophosphamide
750 mg/m^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles.
• doxorubicin
50 mg/m^2 IV, Day 1 of each 21-cycle, 6 cycles.
• prednisone
100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles.
• vincristine
1.4 mg/m^2 IV, Day 1 of each 21-day cycle, 6 cycles.

Locations

Country	Name	City	State
United States	McFarland Clinic	Ames	Iowa
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Cancer Center Department of Hematology	Aurora	Colorado
United States	MSKCC at Basking Ridge	Basking Ridge	New Jersey
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Medical University of SC (MUSC)	Charleston	South Carolina
United States	Northwestern University; Robert H. Lurie Comp Can Ctr	Chicago	Illinois
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Memorial Sloan-Kettering; Cancer Center	Commack	New York
United States	Rocky Mountain Cancer Ctr - Denver (Williams)	Denver	Colorado
United States	cCare	Encinitas	California
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Florida Cancer Specialists; Department of Oncology	Fort Myers	Florida
United States	Onc & Hem Assoc; USO Cent Pharm	Fort Worth	Texas
United States	Aurora Bay Care Medical Center	Green Bay	Wisconsin
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Emerywood Hematology and Onc	High Point	North Carolina
United States	MD Anderson Cancer Center Department of Lymphoma & Myeloma	Houston	Texas
United States	Methodist Hospital Research Institute	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Jewish Cancer Care	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	MT Cancer Inst Fndtn; MT Can Spec	Missoula	Montana
United States	SCRI-Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Onc Hem Assoc of Central IL	Peoria	Illinois
United States	Blue Ridge Cancer Care - Roanoke	Roanoke	Virginia
United States	MSKCC at Mercy Med Ctr	Rockville Centre	New York
United States	Florida Cancer Specialists; Saint Petersburg	Saint Petersburg	Florida
United States	Cancer Therapy & Research Center	San Antonio	Texas
United States	MSKCC at Sleepy Hollow	Sleepy Hollow	New York
United States	Medical Oncology Associates	Spokane	Washington
United States	Willamette Valley Cancer Insitute and Research Center	Springfield	Oregon
United States	USO - Tyler Cancer Ctr	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) 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 IRF using CT scans, PET scans and pertinent clinical information. 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)
Secondary	Overall Response Rate (ORR) as Assessed by the IRF 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 IRF using CT scans, PET scans and pertinent clinical information. 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	Progression-Free Survival (PFS) as Assessed by the Investigator	PFS was defined as the time from the date of the first dose of study treatment until the date of disease progression, relapse, or death from any cause.	From the first dose of study treatment to PFS assessment (up to 64 months)
Secondary	Duration of Response (DOR)	DOR is defined as first occurrence of documented response (CR or PR) until the first occurrence of relapse or progression or death of any cause. CR: disappearance of all evidence of disease. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.	From the response assessment to relapse, progression, or death (up to 64 months)
Secondary	Percentage of Participants With Adverse Events as a Measure of Safety	An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug or other protocol-imposed intervention. Preexisting conditions that worsened during the study were reported as adverse events.	From the first dose of study treatment to end of study (up to 5 years 4 months)
Secondary	Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI)	SDI 120 is a shorter duration infusion of 120 minutes and SDI 90 is shorter duration infusion of 90 minutes. Grade 3 IRR AE: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4 IRR AE: Life-threatening consequences; urgent intervention indicated.	From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
Secondary	Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab	Blood was collected for PK Parameters. 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).	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
Secondary	Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab	T1/2 is the time required for the concentration of the drug to reach half of its original value. Blood was collected for PK Parameters. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in days	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
Secondary	Pharmacokinetics: Clearance (Cl) for Obinutuzumab	Cl is the volume of serum cleared of the drug per unit of time. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in milliliters/day (mL/day).	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
Secondary	Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab	V is the apparent volume in which a drug is distributed in the body. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in milliliters (mL).	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
Secondary	Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day)	Blood was collected for PK parameters. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in in day times micrograms per milliliter (day*µg/mL).	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
Secondary	Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count		Up to approximately 24 months