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....
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07388563.
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.
Lead OrganizationNational Cancer Institute
Principal InvestigatorMax Gordon
