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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Days 1-5 or 1-7 of every cycle (12 cycles): azacitidine subcutaneous or IV at the dose of 75 mg/m2
Cycle 0, Days 1 and 15: abatacept IV infusions at the dose of 5 mg/kg or 10 mg/kg. Cycles 1-6, Day 1: abatacept IV infusions at the dose of 5 mg/kg or 10 mg/kg.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Arm 2: To estimate the CRR of the combination of azacitidine and abatacept.
Complete response rate (CRR) will be evaluated in Arm 2 in participants treated at MTD. CRR will be estimated along with a 95% confidence interval (CI).
Time frame: Day 1 of Cycles 1, 4, 7, 10, EOT/PD visit, every 3 months for years 1-2, every 6 months for years 3-4, once a year for year 5.
Arm 1: To estimate the MTD of the combination of azacitidine and abatacept in relapsed or refractory T-cell lymphoma.
MTD will be determined based on the DLT profile during the DLT window in Arm 1 56 days (cycles 0-1).
Time frame: 56 days (cycles 0-1)
To determine the ORR defined as CR + PR to the combination of azacitidine and abatacept
ORR will be estimated along with a 95% CI. Every report of response rates will contain all participants included in the study.
Time frame: Day 1 of every cycle then at the EOT/PD visit, every 3 months for years 1-2, every 6 months for years 3-4, then once a year until progression, initiation of another line of therapy, or 5 years since treatment initiation.
To determine the safety profile of a combination of azacitidine and abatacept in relapsed or refractory T-cell lymphoma
The number and frequency of adverse events for participants as assessed per CTCAE version 6. Safety will be analyzed by reporting the number of patients experiencing toxicity, classified by type and maximum grade to the experimental regimen.
Time frame: Day 1 through 30 days after the last study intervention was administered or before the initiation of a new anti-cancer treatment, whichever comes first.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.