Azacitidine and Abatacept in Relapsed or Refractory T-Cell Lymphoma

Background: T-cell lymphoma is a blood cancer that affects immune system cells. People tend to survive less than 1 year if this disease does not respond to treatment (is refractory) or comes back after treatment (relapses). Azacitidine and abatacept are 2 drugs that are used to treat other diseases. Researchers want to know if these drugs, used together, can help people with T-cell lymphoma. Objective: To learn if azacitidine combined with abatacept can shrink tumors in people with T-cell lymphoma. Eligibility: People aged 18 years and older with T-cell lymphoma that either came back or did not respond to treatment. Design: Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have imaging scans of their tumors. A sample of tumor tissue may be taken. Azacitidine is injected under the skin of the thigh, abdomen, or upper arm. Abatacept is infused through a needle inserted into a vein in the arm. Participants will receive the study drugs in 28-day cycles for up to 13 cycles. They will come to the clinic for each treatment. They will come to the clinic on day 1 and day 15 of the first cycle. After that, they will come to the clinic on the first 5 or 7 days of each cycle. Each clinic visit will take no more than 8 hours. Imaging scans and other tests will be repeated during the study. Participants will have follow-up visits for up to 5 years after they stop taking the study drugs....

Background: * Relapsed or refractory T-cell lymphoma is typically incurable with a median survival of less than 1 year. Angioimmunoblastic T-cell lymphoma (AITL) is the most commonly defined subtype of T-cell lymphoma and has a similarly poor prognosis. * We have developed the first AITL cell lines that maintain immunophenotypic fidelity with AITL and used these cell lines to identify novel therapies for patients with AITL. * We found that CD28 blockade with the Food and Drug Administration (FDA)-approved rheumatologic agent abatacept, which blocks CD28 signaling, impaired the proliferation of AITL cell lines, and that injection of abatacept into patient-derived xenograft (PDX) models of AITL significantly prolonged their survival. Based on this we conclude that targeting CD28 with abatacept in AITL is a promising, novel therapeutic approach that warrants clinical testing in people with relapsed/refractory (R/R) T-cell lymphoma. * Abatacept can be combined with the deoxyribonucleic acid (DNA) methyltransferase inhibitor azacitidine, which has been shown to be preferentially active in patients with a TET2 mutation, the most common genetic abnormality in patients with AITL. We confirmed that azacitidine indeed inhibits AITL cell lines synergistically with abatacept. Objectives: * Arm 1: To estimate the maximum tolerated dose (MTD) of the combination of azacitidine and abatacept in relapsed or refractory T-cell lymphoma. * Arm 2: To estimate the complete response rate (CRR) of the combination of azacitidine and abatacept. Eligibility: * Participants \>= 18 years with relapsed or refractory T-cell lymphoma after initial systemic treatment. * Adequate organ and marrow function. * Eastern Cooperative Oncology Group (ECOG) performance status \<= 2. Design: * This is a non-randomized, open-label, single-site phase I trial evaluating the combination of azacitidine and abatacept. * Treatment will be delivered in cycles consistent of 28 days. * During Cycle 0 abatacept will be administered intravenously on Days 1 and 15. * During Cycles 1-6 abatacept administered on Day 1 will be combined with subcutaneous azacitidine delivered on Days 1-5 or Days 1-7. * After Cycle 6 participants will be evaluated and participants who have a response will get additional 6 cycles of the monotherapy with azacitidine.