Vincristine Sulfate Liposome Injection with Combination Chemotherapy for Children, Adolescents, and Young Adults with Relapsed Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia and Lymphoma Consortium Trial

Vincristine sulfate liposome injection (VSLI), a liposomal formulation of vincristine, may be better tolerated than standard aqueous vincristine and enable dose intensification. Based on single-agent tolerability, activity, and FDA approval in adults with acute lymphoblastic leukemia (ALL), we tested the safety and feasibility of VSLI as replacement for standard vincristine in the UK ALL R3 mitoxantrone-based four-drug induction (Cohort A), a three-drug anthracycline-free induction (Cohort B), and maintenance chemotherapy (Cohort C) in children and young adults with relapsed/refractory B-cell ALL. Among 29 participants with a median age of 12.4 years (range: 1.8-19.6 years), 16 received Cohort A, eight received Cohort B, and five received Cohort C therapy. Dose level 1 (DL1): 1.5 mg/m and dose level 2 (DL2): 2 mg/m of VSLI, each without a dose cap, were tested. Collectively, the median VSLI dose administered was 1.9 mg (range: 0.71-4.06 mg), and 13 (44.8%) received a dose above the standard 2 mg vincristine dose cap. Dose-limiting toxicities (DLTs) at DL2 were seen in three patients, two in Cohort A and one in Cohort B, prompting further evaluation at DL1 for both cohorts. No DLTs were experienced at DL1. Only DL2 was tested in Cohort C-without DLT. Complete remissions were seen in 14 of 16 (87.5%) participants in Cohort A; three of eight (37.5%) in Cohort B; and one (20%) in Cohort C. VSLI with combination chemotherapy at DL1 was generally well tolerated. Based on the promising response signal in this heavily pretreated population, further study of VSLI is warranted. (ClinicalTrials.gov NCT02879643).