Report of a phase II study of sphingosomal vincristine (SV) in patients with relapsed or refractory Hodgkin’s disease

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6624 Background: Combination therapy is often not an option for multiple relapsed/refractory Hodgkin’s disease patients particularly after salvage high-dose chemotherapy and transplant. Vincristine is a cell cycle-specific anticancer drug, with established activity in Hodgkin’s disease. Sphingosomal vincristine (SV) is a novel sphingosome encapsulated formulation of vincristine, which presents several advantages over regular vincristine. SV has a longer half-life (15 hours versus 15 minutes), can be given uncapped, and shows accumulation in tumor sites in experimental models, providing a rationale for this cell-cycle specific agent. Methods: : SV was evaluated as a single agent for the treatment of patients with relapsed or refractory Hodgkin’s disease including those who failed auto or allogeneic transplantation. SV was administered at 2 mg/m2 (no dose capping) IV over 1 hour every 14 days. Patients were restaged every two cycles, responders continued two cycles beyond their best response to a maximum of 12 cycles. Results: Data is reported on 29 patients, 16 males and 13 females; median age was 32 years (range 19–58). Patients had a median of 4 prior chemotherapy regimens (range 2–10), 20 patients had also received prior radiation therapy and 22/29 pts (76%) failed prior transplant. Patients received a median of 4 cycles of SV (range 1–12). Among 27 patients evaluable, 8 responded with 2 CR, 2 CRu, and 4 PR for an overall response rate (ORR) of 30%. Other patients had stable disease (10 pts) or progression (9 pts). Among the responders the median number of prior therapy was 3 (range 2–6), 6/8 responders failed prior auto transplant. Grade 3 toxicity included: sensory neuropathy (2 pts), constipation (2 pts), pain/myalgia (2 pts), fatigue (2 pts), fever (w/o neutropenia) (1 pt). There was no grade 4 toxicity. Conclusions: SV is a promising agent for the treatment of relapsed/refractory Hodgkin’s disease with a 30% ORR in a heavily pretreated population. This therapy was well tolerated with mostly mild to moderate toxicities reported and few grade 3 toxicities despite the number of prior therapies. The ORR and manageable toxicity observed in this study supports further investigation of SV in this disease. No significant financial relationships to disclose.

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