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.
Locations matching your search criteria
United States
Maryland
Bethesda
National Institutes of Health Clinical CenterStatus: Active
Contact: National Cancer Institute Referral Office
Phone: 888-624-1937
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
