Azacitidine With Rituximab, Vincristine, and Cyclophosphamide in Refractory Lymphoma

Study Overview
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Brief Summary
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This is a phase I, prospective, open label, dose escalation study of azacitidine in combination with rituximab, vincristine, and cyclophosphamide for the treatment of refractory lymphoma. The investigators expect to enroll 12-24 patients in this trial over a 2 year accrual period.

Official Title
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Azacitidine With Rituximab, Vincristine, and Cyclophosphamide in Refractory Lymphoma: A Phase I Trial

Conditions
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Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Azacitidine with rituximab, vincristine, and cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines. Age ≥ 18 years and without a maximum age. All patients of reproductive potential should not plan on conceiving children during the treatment program and must agree to use a medically accepted form of contraception. Women of childbearing potential must have a negative serum pregnancy test within 2 weeks of beginning treatment. Patients must have relapsed lymphoma. ECOG performance status of 2 or better. Exclusion Criteria: Pregnant or breast-feeding at the time of proposed study entry Clinical AIDS or ARS or known positive HIV serology History of malignant neoplasm, other than lymphoma, treated within two years prior to study entry (other than non-melanoma skin cancer or in situ cervical cancer) or where there is current evidence of recurrent or metastatic disease Psychiatric or additive disorders that would preclude obtaining informed consent Serum bilirubin > 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these are attributed to active hemolysis Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels > 2 times ULN Serum creatinine levels > 1.5 times ULN Platelets < 75,000/mm3 Absolute neutrophil count < 1500/mm3 Active infection including viral hepatitis Known or suspected hypersensitivity to mannitol, azacitidine, or rituximab Grade 3 or 4 neuropathy Advanced hepatic tumors Uncompensated heart failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Azacitidine<br> | Drug: Azacitidine with rituximab, vincristine, and cyclophosphamide<br>* Azacitidine cycle days 1-5 Cyclophosphamide cycle days 6-9 Vincristine cycle day 8 Rituximab cycle day 8 Rituximab is only for those patients with CD20+ lymphoma. Azacitidine 25 mg/m2^ Azacitidine 50 mg/m2^ Azacitidine 75 mg/m2^ Azacitidine 100 mg/m2^<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximal tolerated dose (MTD) of azacitidine in combination with rituximab, vincristine, and cyclophosphamide in patients with lymphoma |  | Eight 21 day cycles |