Blood
Blood
5 years ago

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

Laine Atkins, Ahmed Sawas, Codruta Chiuzan, Owen A O'Connor, Mark A Francescone, Matko Kalac, Hye A Kim, Emily Lichtenstein, Changchun Deng, Jennifer Lue, Karen Khan, Renee Lichtenstein, Jennifer E Amengual, Enrica Marchi, Serge Cremers, Lawrence Schwartz, Aishling Rada, Lorenzo Falchi
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.

Publisher URL: http://doi.org/10.1182/blood-2017-09-806737

DOI: 10.1182/blood-2017-09-806737

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