Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL

The peripheral T-cell lymphomas (PTCLs) are rare subtypes of Non-Hodgkin lymphoma (NHL) with unique clinicopathologic features and very unfavorable prognosis. Recently it has been demonstrated that PTCLs are characterized by recurrent mutations in epigenetic operators (e.g. TET2, DNMT3A, and IDH2) and escape from immune surveillance. The safety and toxicity of these combinations will be evaluated throughout the entire study. Dose allocation in Arms A and C will be based upon a continual reassessment method (CRM), and combination allocation in Arm B will be conducted using a DLT-adapted partial order continual reassessment method (POCRM) for dose-finding with combinations of agents. Study Hypothesis: If pralatrexate and/or decitabine functions in an immunomodulatory fashion then priming and modulating the malignant cells and the microenvironment will enhance the antitumor activity of pembrolizumab in patients with PTCLs and CTCLs.