Belinostat in Combination With Azacitidine or Pralatrexate for the Treatment of Relapse or Refractory T-cell Lymphoma

PRIMARY OBJECTIVES: I. To evaluate the safety and feasibility of combining azacitidine with belinostat in R/R nodal TFH cell lymphoma. (Arm A) II. To evaluate the safety and feasibility of combining pralatrexate with belinostat in R/R PTCL and CTCL with large cell transformation. (Arm B) SECONDARY OBJECTIVES: I. To measure the clinical efficacy as measured by overall response rate (ORR), complete response (CR) rate, and time to next treatment (TTNT) of belinostat and azacitidine. (Arm A) II. Patient-reported outcomes as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health37 and Functional Assessment of Cancer Therapy (FACT)-Item GP5 scale. (Arm A) III. To measure the clinical efficacy as measured by ORR, CR rate, and TTNT of belinostat and pralatrexate. (Arm B) IV. Patient-reported outcomes as measured by the PROMIS Global Health37 and FACT-Item GP5 scale. (Arm B) EXPLORATORY OBJECTIVES: I. To measure survival outcomes by progression-free survival (PFS) and overall survival (OS) of belinostat and azacitidine. (Arm A) II. Examine the association between biomarkers (e.g., genomic proofing, minimal residual disease \[MRD\]) and clinical outcomes (ORR, PFS). (Arm A) III. To measure survival outcomes by PFS and OS of belinostat and pralatrexate. (Arm B) IV. Examine the association between biomarkers (e.g., genomic profiling, MRD) and clinical outcomes (ORR, PFS). (Arm B) OUTLINE: Patients are assigned to 1 of 2 arms. ARM A: Patients receive azacitidine subcutaneously (SC) on days 1-5 and belinostat intravenously (IV) over 30-45 minutes on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET), and computed tomography (CT) or PET/CT throughout the study. ARM B: Patients receive pralatrexate SC on days 8 and 15 and belinostat IV over 30-45 minutes on days 1-3 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and FDG-PET, and CT or PET/CT throughout the study. After completion of study treatment, patients in Arm A are followed up at 30 days, every 3 months for up to 2 years, then for up to 5 years. Patients in Arm B are followed up at 30 days, every 3 months for up to one year from start of treatment, every 6 months for up to 2 years then every 5 years.