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NCT Number: NCT01414855

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Cyclophosphamide

Drug

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

Doxorubicin

Drug

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

Prednisone

Drug

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

Vincristine

Drug

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

Primary outcomes

  1. 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.

  2. 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 outcomes

  1. 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.

  2. 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.

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

    Time frame: From the first dose of study treatment to PFS assessment (up to 64 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.

  4. Duration of Response (DOR)

    Time frame: From the response assessment to relapse, progression, or death (up to 64 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. 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.

  5. Percentage of Participants With Adverse Events as a Measure of Safety

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

    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.

  6. 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.

  7. 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).

  8. 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

  9. 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).

  10. 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).

  11. 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).

  12. Pharmacodynamics: Peripheral Blood CD19-positive B-cell Count

    Time frame: Up to approximately 24 months

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2013
Study completion
2016
First posted
Aug 11, 2011
Registry last updated
Apr 25, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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