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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01414855
First Posted: August 11, 2011
Last Update Posted: May 23, 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 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.

Condition Intervention Phase
Lymphoma, B-Cell Drug: obinutuzumab Drug: cyclophosphamide Drug: doxorubicin Drug: prednisone Drug: vincristine Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]
    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.

  • Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]
    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.


Secondary Outcome Measures:
  • Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]
    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.

  • Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]
    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.

  • Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: From the first dose of study treatment to PFS assessment (Up to 28 months) ]
    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.

  • Duration of Response (DOR) [ Time Frame: From the first dose of study treatment to response assessment (Up to 28 months) ]
    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.

  • Percentage of Participants With Adverse Events as a Measure of Safety [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]
    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.

  • Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI) [ Time Frame: From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days) ]

    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.


  • Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab [ Time Frame: 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 ]
    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).

  • Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab [ Time Frame: 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 ]
    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

  • Pharmacokinetics: Clearance (Cl) for Obinutuzumab [ Time Frame: 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 ]
    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).

  • Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab [ Time Frame: 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 ]
    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).

  • Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day) [ Time Frame: 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 ]
    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).

  • Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count [ Time Frame: Up to approximately 24 months ]

Enrollment: 100
Actual Study Start Date: August 31, 2011
Study Completion Date: December 23, 2016
Primary Completion Date: December 31, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: obinutuzumab + CHOP
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
1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15.
Drug: cyclophosphamide
750 mg/m^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles.
Drug: doxorubicin
50 mg/m^2 IV, Day 1 of each 21-cycle, 6 cycles.
Drug: prednisone
100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles.
Drug: vincristine
1.4 mg/m^2 IV, Day 1 of each 21-day cycle, 6 cycles.

  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:

  • 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
  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): NCT01414855


  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3300
United States, California
cCare
Encinitas, California, United States, 92024
United States, Colorado
University of Colorado Cancer Center Department of Hematology
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Ctr - Denver (Williams)
Denver, Colorado, United States, 80218
United States, Connecticut
Norwalk Hospital
Norwalk, Connecticut, United States, 06856
United States, Florida
Florida Cancer Specialists; Department of Oncology
Fort Myers, Florida, United States, 33901-8101
Florida Cancer Specialists; Saint Petersburg
St Petersburg, Florida, United States, 33719
United States, Georgia
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, United States, 30060
United States, Idaho
Kootenai Medical Center
Coeur D'alene, Idaho, United States, 83814
United States, Illinois
Northwestern University; Robert H. Lurie Comp Can Ctr
Chicago, Illinois, United States, 60611
Onc Hem Assoc of Central IL
Peoria, Illinois, United States, 61615-7828
United States, Iowa
McFarland Clinic
Ames, Iowa, United States, 50010
United States, Kentucky
Jewish Cancer Care
Louisville, Kentucky, United States, 40245
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-0934
United States, Montana
MT Cancer Inst Fndtn; MT Can Spec
Missoula, Montana, United States, 59802
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89128
United States, New Jersey
MSKCC at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New Mexico
San Juan Oncology Associates
Farmington, New Mexico, United States, 87401
United States, New York
Memorial Sloan-Kettering; Cancer Center
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
MSKCC at Mercy Med Ctr
Rockville Centre, New York, United States, 11570
MSKCC at Sleepy Hollow
Sleepy Hollow, New York, United States, 10591
United States, North Carolina
Emerywood Hematology and Onc
High Point, North Carolina, United States, 27262
United States, Oregon
Willamette Valley Cancer Insitute and Research Center
Springfield, Oregon, United States, 97477
United States, South Carolina
Medical University of SC (MUSC)
Charleston, South Carolina, United States, 29425
United States, Tennessee
SCRI-Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Onc & Hem Assoc; USO Cent Pharm
Fort Worth, Texas, United States, 76177
MD Anderson Cancer Center Department of Lymphoma & Myeloma
Houston, Texas, United States, 77030
Methodist Hospital Research Institute
Houston, Texas, United States, 77030
Cancer Therapy & Research Center
San Antonio, Texas, United States, 78229
USO - Tyler Cancer Ctr
Tyler, Texas, United States, 75702
United States, Virginia
Blue Ridge Cancer Care - Roanoke
Roanoke, Virginia, United States, 24014
United States, Washington
Medical Oncology Associates
Spokane, Washington, United States, 99208
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, United States, 98684
Yakima Valley Memorial Hospital/North Star Lodge
Yakima, Washington, United States, 98902
United States, Wisconsin
Aurora Bay Care Medical Center
Green Bay, Wisconsin, United States, 54311
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01414855     History of Changes
Other Study ID Numbers: GAO4915g
First Submitted: August 10, 2011
First Posted: August 11, 2011
Results First Submitted: February 5, 2015
Results First Posted: March 19, 2015
Last Update Posted: May 23, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Liposomal doxorubicin
Obinutuzumab
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents