This partially randomized phase I trial studies the side effects and best dose of ipilimumab when given together with rituximab in treating patients with B-cell lymphoma that has returned or has not responded to treatment. Monoclonal antibodies, such as ipilimumab and rituximab, may interfere with the ability of cancer cells to grow and spread.
PRIMARY OBJECTIVES: I. To determine a recommended phase II dose for ipilimumab in combination with rituximab. SECONDARY OBJECTIVES: I. To obtain preliminary information on the effect of adding ipilimumab to rituximab in regard to: immune response; clinical anti-tumor response/overall remission rate (ORR) (complete remission + partial remission); progression free survival (PFS). OUTLINE: This is a dose-escalation study of ipilimumab followed by a randomized study. PART I: INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes once every 3 weeks for 12 weeks and rituximab IV over 2-6 hours once weekly for 4 weeks. MAINTENANCE: Patients receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year. PART II: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4
Tables will be created to summarize the toxicities and side effects by dose, course, organ and severity.
Time frame: Up to 12 months
Immune response as measured by the frequency of activated T-cells, absolute lymphocyte count, antibody dependent cell-mediated cytotoxicity, and kinetics and magnitude of B-cell depletion
Regression methods (adapted for repeated measures) will be used to describe the changes over time. In addition to summarizing the changes over time within each arm, these regression models will contain contrasts to compare the two arms in terms of changes.
Time frame: Up to 14 weeks
Clinical anti-tumor response (complete response and partial response as per international workshop lymphoma response criteria [Cheson 2007])
Time frame: Up to 12 months
Progression-free survival
Progression-free survival will be summarized using Kaplan-Meier plots.
Time frame: From when the patient started treatment to the time the patient is first recorded as having disease relapse/progression, or to the date of death if the patient dies due to causes other than disease progression, assessed up to 12 months
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South Pasadena, California, United States
Washington University School of Medicine
St Louis, Missouri, United States
Duke University Medical Center
Durham, North Carolina, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States