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

Nirali N. Shah, Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
Eric S. Schafer, Division of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Cancer and Hematology Center, Houston, Texas, USA.
Yueh-Yun Chi, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Jemily Malvar, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Kenneth M. Heym, Hematology and Oncology, Cook Children's Medical Center, Fort Worth, Texas, USA.
Andrew E. Place, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
Melissa Burns, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
Bill H. Chang, Division of Hematology and Oncology, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USA.
Tamra Slone, Children's Medical Center, UT Southwestern, Dallas, Texas, USA.
Anupam Verma, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Nathan Gossai, Center for Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota, USA.
Peter H. Shaw, Division of Hematology and Oncology, Department of Pediatrics, Children's Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Michael J. Burke, Division of Hematology and Oncology, Department of Pediatrics, Children's Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Michelle Hermiston, Pediatric Hematology/Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
Reuven J. Schore, Division of Pediatric Oncology, Children's National Hospital/George Washington University SMHS, Washington, District of Columbia, USA.
Todd Cooper, Seattle Children's Cancer and Blood Disorders Center, University of Washington, Seattle, Washington, USA.
Melinda Pauly, Department of Pediatric Hematology Oncology, Emory University and Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Teresa Rushing, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Paul Jarosinski, Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
Ellynore Florendo, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Bonnie Yates, Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
Brigitte C. Widemann, Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
Cody J. Peer, Clinical Pharmacology Laboratory, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
William D. Figg, Clinical Pharmacology Laboratory, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Lewis B. Silverman, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Columbia University Medical Center, New York, New York, USA.
Deepa Bhojwani, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Alan S. Wayne, Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Document Type

Journal Article

Publication Date

2-12-2025

Journal

Pediatric blood & cancer

DOI

10.1002/pbc.31584

Keywords

acute lymphoblastic leukemia; combination chemotherapy; relapse; vincristine

Abstract

INTRODUCTION: Vincristine sulfate liposome injection (VSLI), a liposomal formulation of vincristine, may be better tolerated than standard aqueous vincristine and enable dose intensification. PROCEDURES: 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. RESULTS: 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. CONCLUSION: Based on the promising response signal in this heavily pretreated population, further study of VSLI is warranted. (ClinicalTrials.gov NCT02879643).

Department

Pediatrics

Link to Full Text

Share

COinS