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

Purpose: Pralatrexate is a folic acid analogue metabolic inhibitor similar to methotrexate, which has shown tolerability and efficacy with an overall response rate of 45% in a phase I dose deescalation study of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Experimental Design: The object of this phase I/II open-label, multicenter clinical trial was to determine the 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 intravenous 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 2 months. Results: At the MTD of 15 mg/m² bexarotene and 15 mg/m² pralatrexate, the response rate was 60% [4 complete responses (CR), 14 partial responses (PR)], the maximum observed response duration was 28.9þ months, and duration of response for 4 CRs ranged from 9.0 to 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.