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 is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01414855
First received: August 10, 2011
Last updated: March 17, 2015
Last verified: March 2015
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: August 2011
Estimated Study Completion Date: February 2017
Primary Completion Date: December 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414855

  Show 36 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01414855     History of Changes
Other Study ID Numbers: GAO4915g
Study First Received: August 10, 2011
Results First Received: February 5, 2015
Last Updated: March 17, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Obinutuzumab
Vincristine
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on June 29, 2015