Phase 1/2a Study of Anti-PD-L1 Monoclonal Antibody Durvalumab in Combination With Pralatrexate and Romidepsin, Oral 5-Aza and Romidepsin, Romidepsin Alone, or Oral 5-Azacitidine for Treatment of Patients With Relapsed and Refractory PTCL
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.
• 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:
‣ Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2 x institutional upper limit of normal (ULN); total bilirubin ≤ 1.5 x ULN (AST, ALT, and total bilirubin ≤ 3 × ULN in subjects with documented Gilbert's syndrome or hyperbilirubinemia clearly attributed to lymphoma involvement of the liver);
⁃ Creatinine levels \< 2 mg/dL; or creatinine clearance \> 40 mL/min
⁃ Absolute neutrophil count (ANC) \> 1,000/μL; platelet count \> 75,000/μL
⁃ Negative urine or serum pregnancy test for women of childbearing potential. All women of childbearing potential must agree to use an effective barrier method of contraception (either an intrauterine device (IUD) or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month after discontinuation of the study drugs. Male subjects should use effective barrier method of contraception during the treatment period and for at least 3 months after discontinuation of the study drugs.
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to adhere to the study visit schedule and other protocol requirements