Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Jun;63(6):997-1005.
doi: 10.1002/pbc.25937. Epub 2016 Feb 17.

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  1 , Melinda S Merchant  1 , Diane E Cole  1 , Nalini Jayaprakash  1 , Donna Bernstein  1 , Cindy Delbrook  1 , Kelly Richards  1 , Brigitte C Widemann  1 , Alan S Wayne  1   2
Affiliations
Clinical Trial

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 et al. Pediatr Blood Cancer. 2016 Jun.

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.

Keywords: Marqibo®; acute lymphoblastic leukemia; pediatric; phase I.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Please see the associated Author Disclosure Declaration forms and responses to additional questions for details for all co-authors.

Figures

Fig. 1.
Fig. 1.
Pharmacokinetics. Relationship of patient age to vincristine clearance (A) and terminal half-life (B). Comparison of clearance (C) and terminal half-life (D) between those subjects less than 13 years versus those 13 years and older. Example of representative plasma concentration-time curves, demonstrating variability in vincristine exposure in two patients treated at dose level 1 (1.75 mg/m2/dose) (E).
Fig. 2.
Fig. 2.
Clinical activity. Twelve-year-old male with refractory ALL and posttransplant relapse attained a minimal residual disease negative complete response after two cycles (A). Rapid reduction of absolute peripheral blast count after single dose of VSLI in two subjects with chemotherapy-refractory ALL (B) Subject 13: 5-year-old female (B1); subject 10: 5-year-old male (B2).
See this image and copyright information in PMC

References

    1. Weiden PL, Wright SE. Vincristine neurotoxicity. N Engl J Med 1972;286:1369–1370. - PubMed
    1. Bowman WP, Larsen EL, Devidas M, Linda SB, Blach L, Carroll AJ, Carroll WL, Pullen DJ, Shuster J, Willman CL, Winick N, Camitta BM, Hunger SP, Borowitz MJ. Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: Results of Children’s Oncology Group trial P9906. Pediatr Blood Cancer 2011;57:569–577. - PMC - PubMed
    1. Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reama G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: A report from the Children’s Oncology Group. Blood 2011;118:243–251. - PMC - PubMed
    1. Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, Weiss AR. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized ewing sarcoma: A report from the Children’s Oncology Group. J Clin Oncol 2012;30:4148–4154. - PMC - PubMed
    1. Nachman J, Sather HN, Gaynon PS, Lukens JN, Wolf L, Trigg ME. Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: A report from the Children’s Cancer Group. J Clin Oncol 1997;15:2222–2230. - PubMed

Publication types