High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial

J Adolesc Young Adult Oncol. 2018 Oct;7(5):546-552. doi: 10.1089/jayao.2018.0041. Epub 2018 Sep 21.

Abstract

Purpose: A study of vincristine sulfate (VCR) liposome injection (VSLI) was conducted in patients with advanced, relapsed, or refractory, Philadelphia chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A retrospective subgroup analysis of the results was performed to evaluate the safety and efficacy of VSLI in the adolescent and young adult (AYA) patients.

Methods: Of the 65 patients treated in the pivotal Phase 2 Study HBS407 (NCT00495079), 44 patients were aged ≤39 years (median 27 [range 19-39] years) and were included in this analysis. Patients received VSLI (2.25 mg/m2 intravenously every 7 ± 3 days) without dose capping or concurrent steroid administration in continuous 28-day cycles.

Results: VSLI was well tolerated in the AYA patients over a median of 5 (range 1-15) doses administered. One-third of patients (36%) experienced treatment-related serious adverse events (AEs) with peripheral neuropathy (7%), tumor lysis syndrome (7%), and febrile neutropenia (5%) in >1 patient. Neuropathy-associated AEs occurred in 82% patients; no neuropathy-related deaths occurred. The rate of complete remission (CR) (with or without complete blood count recovery) by investigator assessment was 25% in AYA patients, and the overall response rate was 39%. Median leukemia-free survival in AYA patients attaining CR was 135 (range 32-463) days, and median overall survival was 141 (range 13-620) days.

Conclusion: VSLI provided a meaningful clinical benefit to AYA patients with ALL, and its safety profile was comparable to that of VCR despite the delivery of higher doses (individual and cumulative).

Keywords: acute lymphoblastic leukemia; vincristine sulfate liposome injection.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Injections / methods*
  • Liposomes / pharmacology
  • Liposomes / therapeutic use*
  • Male
  • Philadelphia Chromosome / drug effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Recurrence
  • Treatment Outcome
  • Vincristine / pharmacology
  • Vincristine / therapeutic use*
  • Young Adult

Substances

  • Liposomes
  • Vincristine

Associated data

  • ClinicalTrials.gov/NCT00495079