Durvalumab in Different Combinations With Pralatrexate, Romidepsin and Oral 5-Azacitidine for Lymphoma
Trial Parameters
Brief Summary
This is an open-label, Phase 1/2a, dose-finding study with an initial phase 1 portion, articulated in four separate treatment arms, followed by a dedicated phase 2 for qualifying treatment Arm(s). The primary objective of the Phase 1 portion is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of: Durvalumab, oral 5-azacitidine, and romidepsin (Arm A); durvalumab, pralatrexate, and romidepsin (Arm B); durvalumab and romidepsin (Arm C); or durvalumab and oral 5-azacitidine (Arm D), in patients with peripheral T-cell lymphoma (PTCL). The safety and toxicity profile of these combinations will be evaluated throughout the entire study. If one or more of the combinations in Arms A, B, C, or D are found to be feasible and an MTD is established, the phase 2 portion of the study will be initiated for the combination(s) with the strongest efficacy signal provided acceptable toxicity.
Eligibility Criteria
Inclusion Criteria (these criteria apply to both the phase 1 and phase 2 portion of the study) * Age \>18 years at the time of signing the informed consent * Patients must have histologically confirmed newly diagnosed (ND) or Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL) defined according to the 2016 World Health Organization (WHO) classification criteria. * Patients with R/R PTCL who have received at least one previous line of therapy are eligible to be enrolled in this study. * Patients who are candidate for an autologous or allogeneic stem cell transplantation (SCT) will be allowed to receive the study drugs as a "bridge" to transplantation. * Evaluable (phase 1) or measurable (phase 2) disease. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Patients must have adequate organ and marrow function as defined by: 1. Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2 x institutional upper limit of normal (ULN); total bilirubin ≤ 1.5 x