Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma
CD20 Positive, Recurrent B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for CD20 Positive
Eligibility Criteria
Inclusion Criteria:
- Previously treated, histologically confirmed cluster of differentiation (CD)20+ B cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies or extra nodal biopsies; fine needle aspirates are not acceptable
- All patients must be informed of the investigative nature of the clinical trial and give written informed consent in accordance with institutional and federal guidelines
- Able to adhere to the study visit schedule and other protocol requirements
- Karnofsky >= 70%
- Life expectancy expected to be greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 50,000/mcL
- Total bilirubin =< 2.0 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Serum creatinine =< 2.0 x upper limit of normal OR calculated creatinine clearance >= 30 ml/min/1.73 M^2 by the modified Cockcroft and Gault formula OR creatinine clearance >= 30 mL/min obtained from a 24-hour urine collection
- At least one measurable lesion according to international workshop lymphoma response criteria; there must be measurable lymphadenopathy to follow with serial exam and/or imaging
- All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
- Patients must have evidence of progression of disease during or after last treatment
- Submission of original biopsy for review and verification by participating center hematopathologist
- Disease free of prior malignancies for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients with a history of prior treatment with ipilimumab
- Patients with a history of prior treatment with an anti-programmed cell death (PD) 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have intervened since the therapy; patients who have received prior vaccine therapy are eligible
- Patients who are receiving any other investigational agents
- Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)
- Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
- Patients with known uncontrolled brain metastases are excluded; however, patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
- Patients on systemic corticosteroids (except for patients on stable doses of hormone replacement therapy such as hydrocortisone), or other immunosuppressants (e.g., infliximab, mycophenolate mofetil) are excluded
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections are excluded
- Pregnant women are excluded from this study
- HIV-positive patients on combination antiretroviral therapy are ineligible
- Rituximab within six weeks
Sites / Locations
- City of Hope Comprehensive Cancer Center
- USC / Norris Comprehensive Cancer Center
- University of California Davis Comprehensive Cancer Center
- City of Hope South Pasadena
- Washington University School of Medicine
- Duke University Medical Center
- Penn State Milton S Hershey Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (ipilimumab and rituximab)
Arm B (ipilimumab and rituximab)
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.
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.