A Phase I Trial of 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....
• Participants must have a histologically or cytologically confirmed T-cell lymphoma confirmed by the Laboratory of Pathology (LP), NCI. The one of the following T-cell lymphomas are included:
‣ Peripheral T-cell lymphoma not otherwise specified (PTCL, NOS)
⁃ Angioimmunoblastic T-cell lymphoma (AITL)
⁃ T-follicular helper (TFH) lymphoma
⁃ Anaplastic large cell lymphoma (ALCL)
⁃ Enteropathy-associated T-cell lymphoma (EATL)
⁃ Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
⁃ Adult T-cell leukemia/lymphoma (ATLL)
⁃ Other T-cell lymphoma (TCL)
• Participants must have a disease that is relapsed or refractory after initial systemic treatment.
• Participants must have evaluable disease on screening imaging or by laboratory assessment.
• Age \>= 18 years.
• ECOG performance status \<= 2.
• Participants must have adequate organ and marrow function as defined below:
‣ Absolute neutrophil count (ANC) / \>= 1,000 cells/mcL OR \>= 500 cells/mcL if bone marrow involvement with lymphoma
⁃ Platelets / \>= 50,000 cells/mcL OR \>= 25,000 cells/mcL if bone marrow involvement with lymphoma
⁃ Hemoglobin / \>= 8 g/dL (transfusions permitted)
⁃ Renal function / Serum creatinine \<= 2 mg/dL OR Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2 as estimated by the Modification of Diet in Renal Disease (MDRD).
• Note: there is no limit if involved by lymphoma.
• If not on target, a 24-hour urine creatinine clearance can be used to directly measure creatinine clearance.
⁃ Total bilirubin / \<= 1.5 x upper limit of normal (ULN)
⁃ Aspartate Aminotransferase (AST) / \<= 3.0 x ULN
⁃ Alanine Aminotransferase (ALT) / \<= 3.0 x ULN
⁃ Prothrombin time (PT) / \<1.5 x ULN
⁃ Activated partial thromboplastin time (aPTT) / \<1.5 x ULN; \< 5.0 x ULN if the aPTT is prolonged because of a positive Lupus Anticoagulant
• International normalized ratio (INR) / \<1.5 x ULN
• Participants, seropositive for human immunodeficiency virus (HIV), must have an undetectable HIV viral load.
• Participants, seropositive for hepatitis C virus (HCV) infection, must have been treated and have an undetectable HCV viral load.
• Participants who are hepatitis B core antibody (HBcAb) positive must have a hepatitis B virus (HBV) viral load result \<100 IU/mL. Note: participants who are hepatitis B surface antigen (HBsAg) positive are excluded.
⁃ Participants with detectable Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) by polymerase chain reaction will be eligible provided they do not have end organ dysfunction from EBV or CMV infection.
⁃ Participants with pulmonary disease such as chronic obstructive pulmonary disease and non-infectious liver disease who otherwise meet the requirements.
⁃ Women of child-bearing potential (WOCBP) must agree to use effective methods of contraception (barrier, hormonal, surgical sterilization, abstinence) during the study treatment and for 6 months after the completion of the study treatment. Note: WOCBP is defined as any woman who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.
⁃ Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) during the study treatment and for 3 months after the completion of the study treatment. These men must not freeze or donate sperm within the same period.
⁃ Nursing participants must be willing to discontinue nursing from study treatment initiation through six (6) months after the last dose of the study drug(s).
⁃ Ability of the participant to understand and the willingness to sign a written informed consent document.