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

Pediatr Blood Cancer. 2020 May;67(5):e28112. doi: 10.1002/pbc.28112. Epub 2020 Jan 15.

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.

Keywords: CAT-8015; moxetumomab; pediatric; pharmacokinetics; safety.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bacterial Toxins / administration & dosage*
  • Bacterial Toxins / adverse effects
  • Bacterial Toxins / pharmacokinetics*
  • Biomarkers, Tumor / blood*
  • Child
  • Child, Preschool
  • Exotoxins / administration & dosage*
  • Exotoxins / adverse effects
  • Exotoxins / pharmacokinetics*
  • Female
  • Humans
  • Infant
  • Male
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / blood
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Recurrence

Substances

  • Bacterial Toxins
  • Biomarkers, Tumor
  • Exotoxins
  • immunotoxin HA22