Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia

Nirali N. Shah, Deepa Bhojwani, Keith August, André Baruchel, Yves Bertrand, Jessica Boklan, Luciano Dalla-Pozza, Robyn Dennis, Nobuko Hijiya, Franco Locatelli, Paul L. Martin, Françoise Mechinaud, John Moppett, Susan R. Rheingold, Claudine Schmitt, Tanya M. Trippett, Meina Liang, Kemal Balic, Xia Li, Inna VainshteinNai Shun Yao, Ira Pastan, Alan S. Wayne

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti-CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy. Procedure: This international, multicenter, phase 2 study enrolled children with relapsed/refractory B-cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21-day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations. Results: Thirty-two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment-related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment-related death (n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS. Conclusions: Despite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.

Original languageEnglish
Article numbere28112
JournalPediatric Blood and Cancer
Volume67
Issue number5
DOIs
Publication statusPublished - May 1 2020

Keywords

  • CAT-8015
  • moxetumomab
  • pediatric
  • pharmacokinetics
  • safety

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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