Phase II study of sphingosomal vincristine in patients with recurrent or refractory adult acute lymphocytic leukemia

BACKGROUND. Outcomes with salvage therapy for patients with recurrent or refractory acute lymphocytic leukemia (ALL) are poor, with complete response (CR) rates reported to be 20-30% and a median survival ranging from 2-6 months. New agents are needed to reduce the recurrence rate after frontline chemotherapy. Vincristine is an important component of ALL therapy. In animal models, the encapsulation of vincristine into sphingomyelin liposomes or "sphingosomes" for injection (SV) has improved efficacy compared with conventional vincristine. METHODS. A Phase II clinical trial of single-agent SV given at a dose of 2.0 mg/m² every 2 weeks was conducted in patients with recurrent or refractory ALL. Approximately half of the 16 patients who received SV had a first CR duration of less than 1 year, 19% had failed standard induction chemotherapy, and 50% had Philadelphia chromosome-positive disease. SV was the first salvage attempt in 69% of the patients. RESULTS. The overall response rate in the 14 evaluable patients was 14% (1 CR and 1 partial response). Five patients (36%) had transient reductions in bone marrow leukemia infiltrate with subsequent regrowth of the leukemia between SV infusions. Toxicity with limited treatment (median number of doses was two; range, one to five doses) was minimal with expected peripheral neuropathy. CONCLUSIONS. Further study of SV in patients with ALL is warranted. A Phase I-II clinical trial of weekly SV with pulse dexamethasone currently is ongoing.