Investigational treatment options in phase I and phase II trials for relapsed or refractory acute lymphoblastic leukemia in pediatric patients

Julie M. Asare, Cara A. Rabik, Bradley Muller, Patrick A. Brown, Stacy Cooper

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Upfront treatment of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) results in cure rates of 60–95%, depending on risk factors. However, patients with refractory or relapsed B-ALL or T-ALL have much worse outcomes with conventional chemotherapy, hence treatment of these cohorts with novel agents is a priority. Areas Covered: This paper reviews early phase clinical trials in pediatric leukemia. Investigational antibody therapy, chimeric antigen receptor T-cell (CAR-T), and other targeted therapies are examined. The authors discuss the mechanisms of action, side effects, trial designs, and outcomes and reflect on potential research directions. PubMed and Clinicaltrials.gov were searched from 2010 to present, using keywords ‘lymphoblastic leukemia’ with filters for pediatric age, Phase 1 clinical trial and Phase 2 clinical trial. Expert Opinion: Pediatric patients with relapsed or refractory leukemia often do not derive additional benefit from intensified conventional chemotherapy approaches which have arguably been maximized in the upfront setting. Therefore, novel approaches, such as immunotherapy and targeted agents should be prioritized. Progress will require commitment from pharmaceutical companies regarding these orphan diagnoses and acknowledgment from regulatory bodies that outcomes are suboptimal with conventional chemotherapy.

Original languageEnglish (US)
Pages (from-to)611-620
Number of pages10
JournalExpert Opinion on Investigational Drugs
Volume30
Issue number6
DOIs
StatePublished - 2021

Keywords

  • B-ALL
  • CAR T-cells
  • T-ALL
  • acute lymphoblastic leukemia
  • blinatumomab
  • daratumumab
  • inotuzumab
  • venetoclax

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Investigational treatment options in phase I and phase II trials for relapsed or refractory acute lymphoblastic leukemia in pediatric patients'. Together they form a unique fingerprint.

Cite this