A phase II study of the tolerability and activity of weekly vincristine sulfate liposomes injection (VSLI) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second relapse or progressing following two antileukemia treatment lines

Abstract

7046 Background: VSLI (Marqibo) is a nanoparticle formulation of vincristine sulfate (VCR) encapsulated in sphingomyelin/cholesterol liposomes called Optisomes. The optisomal formulation lends itself to an improved pharmacokinetic profile and enhanced tumor penetration and concentration. Preclinical studies of VSLI showed enhanced efficacy versus standard VCR in a variety of solid and hematologic malignancies. VSLI has a maximum tolerated dose of 2.25 mg/m2 with no dose cap, while conventional VCR is dosed at 1.4 mg/m2 with a 2 mg dose cap. A previous study in relapsed ALL showed a complete response rate of 19%, warranting further study. Methods: Eligible adult subjects received single agent intravenous VSLI at a dose of 2.25 mg/m2 weekly with no dose cap. This international, multicenter, single-arm study will enroll approximately 56 subjects. Major endpoints include response rate and overall survival (OS). An interim analysis was planned following enrollment of 29 evaluable subjects. Results: 29 heavily pretreated subjects received ≥ 1 dose of VSLI. To date, at least 9 of 29 subjects had clearing of leukemic blasts and achievement of an M1 bone marrow. Based on preliminary data, the median OS is estimated to be 7.5 months (95% CI: 4.7–10.5) using the Kaplan-Meier method. The most frequent related adverse event (AE) was peripheral neuropathy (PN) (48%), half of which was grade 3. No grade 4 PN was reported. Six subjects had 8 treatment-associated grade 4 AEs of neutropenia (4), thrombocytopenia (2), anemia (1), and inappropriate antidiuretic hormone secretion (1). Conclusions: These results are encouraging, as VSLI was given as a single agent to a heavily pretreated patient population who nearly universally received prior VCR. This population typically has a very low response rate to anti-leukemia therapies. Early OS data compares favorably to an historical median OS of ∼ 2 months (8.7 weeks) in a second salvage population (data on file, M. D. Anderson). VSLI was well tolerated in these patients in the context of universal prior vincristine treatment. [Table: see text]