Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®): Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias

Nirali N. Shah, Melinda S. Merchant, Diane E. Cole, Nalini Jayaprakash, Donna Bernstein, Cindy Delbrook, Kelly Richards, Brigitte C. Widemann, Alan S. Wayne

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Vincristine sulfate liposome injection (VSLI; Marqibo®) is an encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical trials in adults have demonstrated safety, tolerability, and activity, leading to Food and Drug Administration (FDA) approval for adults with relapsed acute lymphoblastic leukemia (ALL). Pediatric experience with VSLI is limited.

PROCEDURE: This single center, phase I dose escalation study examined the safety, toxicity, maximum tolerated dose, and pharmacokinetics of VSLI administered weekly to pediatric patients age <21 years with relapsed or chemotherapy-refractory solid tumors or leukemia.

RESULTS: Twenty-one subjects were treated in total. Median age was 13.3 years (range 2-19). Fourteen subjects completed one 28-day cycle of therapy and five subjects completed more than one cycle. No subject experienced dose-limiting toxicity (DLT) at the first dose level (1.75 mg/m(2) /dose, dose range: 2-3.7 mg). At the second dose level (2.25 mg/m(2) /dose, dose range: 1.3-4.5 mg), one subject had transient dose-limiting grade 4 transaminase elevation, and this dose level was expanded with no additional DLT observed. The second dose level then opened to an expansion phase to evaluate activity in ALL. Clinical activity included minimal residual disease negative complete remission in one subject with ALL and stable disease in nine subjects. Clearance of total vincristine was found to be approximately 100-fold lower in comparison to published data using standard vincristine.

CONCLUSIONS: Children tolerate 2.25 mg/m(2) /dose of weekly VSLI (the adult FDA-approved dose) with evidence for clinical activity without dose-limiting neurotoxicity. Future plans include studying VSLI as substitution for standard vincristine with combination chemotherapy in children with ALL.

Original languageEnglish (US)
Pages (from-to)997-1005
Number of pages9
JournalPediatric Blood and Cancer
Volume63
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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Vincristine
Liposomes
Young Adult
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Injections
United States Food and Drug Administration
Neoplasms
Pediatrics
Drug Approval
Safety
Maximum Tolerated Dose
Sphingomyelins
Residual Neoplasm
Transaminases
Combination Drug Therapy
Pharmacokinetics
Cholesterol
Clinical Trials
Drug Therapy

Keywords

  • acute lymphoblastic leukemia
  • Marqibo®
  • pediatric
  • phase I

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)
  • Hematology
  • Oncology

Cite this

Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®) : Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias. / Shah, Nirali N.; Merchant, Melinda S.; Cole, Diane E.; Jayaprakash, Nalini; Bernstein, Donna; Delbrook, Cindy; Richards, Kelly; Widemann, Brigitte C.; Wayne, Alan S.

In: Pediatric Blood and Cancer, Vol. 63, No. 6, 01.06.2016, p. 997-1005.

Research output: Contribution to journalArticle

Shah, NN, Merchant, MS, Cole, DE, Jayaprakash, N, Bernstein, D, Delbrook, C, Richards, K, Widemann, BC & Wayne, AS 2016, 'Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®): Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias', Pediatric Blood and Cancer, vol. 63, no. 6, pp. 997-1005. https://doi.org/10.1002/pbc.25937
Shah, Nirali N. ; Merchant, Melinda S. ; Cole, Diane E. ; Jayaprakash, Nalini ; Bernstein, Donna ; Delbrook, Cindy ; Richards, Kelly ; Widemann, Brigitte C. ; Wayne, Alan S. / Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®) : Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias. In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 6. pp. 997-1005.
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