Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma
Mené sur 34 patients atteints d'un lymphome T cutané réfractaire ou récidivant, cet essai de phase I/II évalue la dose maximale tolérée et la dose recommandée de pralatrexate combiné au bexarotène dispensé par voie orale
Purpose:Pralatrexate is a folic acid analog metabolic inhibitor similar to methotrexate,that has shown tolerability and efficacy with an overall response rate of 45% in a phase 1 dose de-escalation study of patients with relapsed/refractory cutaneous T-cell lymphoma CTCL. Experimental Design: The object of this phase I/II open-label, multi-center clinical trial was to determine the maximum tolerated dose (MTD) and recommended dose of pralatrexate plus oral bexarotene in 34 patients with relapsed/refractory CTCL who had failed prior systemic therapies. Pralatrexate was administered by IV push at 15 mg/m2 given weekly 3 weeks out of 4 weeks with daily oral bexarotene (150 or 300 mg/m2), levothyroxine, atorvastatin, folate, and with B12 every two months. Results: At the maximum tolerated dose (MTD), the response rate was 60% (4 CR, 14 PR), the maximum observed response duration was 28.9+ months, and duration of response for 4 CRs ranged from 9.0-28.3 months. The median progression free survival was 12.8 months (0.5-29.9). Mucositis was the most common adverse event. Conclusions: The combination of pralatrexate (15 mg/m2) and oral bexarotene (150 mg/m2) is active with high response rates and minimal toxicity for cutaneous T-cell lymphomas.