A phase I study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma.

A phase I study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma.

Blood. 2017 Nov 15;:

Authors: Amengual JE, Lichtenstein R, Lue J, Sawas A, Deng C, Lichtenstein E, Khan K, Atkins L, Rada A, Kim HA, Chiuzan C, Kalac M, Marchi E, Falchi L, Francescone MA, Schwartz L, Cremers S, O'Connor OA

Abstract
The peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy insensitivity and poor prognosis. Romidepsin and pralatrexate were approved by the U.S. FDA for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy of the combination in preclinical models of PTCL, we initiated a phase I study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma (ClinicalTrials.gov (NCT01947140)). This was a single institution dose-escalation phase I study of pralatrexate plus romidepsin designed to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile and response rates. Patients were treated with pralatrexate 10 mg/m(2) to 25 mg/m(2), and romidepsin 12mg/m(2) to 14 mg/m(2) on one of three schedules: (1) QWx3 Q28D; (2) QWx2 Q21D; (3) QOW Q28D. Treatment continued until progression, withdrawal of consent, or medical necessity. Response was assessed using the Lugano Classification. Twenty-nine patients were enrolled and evaluable for toxicity. Co-administration of pralatrexate and romidepsin was safe and well tolerated. There were 3 DLTs consisting of 2 Grade 3 oral mucositis and 1 Grade 4 sepsis. The RP2D was defined as pralatrexate 25 mg/m(2) and romidepsin 12 mg/m(2) QOW. Twenty-three patients were evaluable for response. The ORR across all patients was 57% (13/23); and in PTCL was 71% (10/14). The phase I study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase II study in PTCL will determine the efficacy of the combination on the QOW dose schedule.

PMID: 29141948 [PubMed - as supplied by publisher]

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