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


Authors: Shah, N. N.; Bhojwani, D.; August, K.; Baruchel, A.; Bertrand, Y.; Boklan, J.; Dalla-Pozza, L.; Dennis, R.; Hijiya, N.; Locatelli, F.; Martin, P. L.; Mechinaud, F.; Moppett, J.; Rheingold, S. R.; Schmitt, C.; Trippett, T. M.; Liang, M.; Balic, K.; Li, X.; Vainshtein, I.; Yao, N. S.; Pastan, I.; Wayne, A. S.
Article Title: Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia
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. © 2020 Wiley Periodicals, Inc.
Keywords: adolescent; child; clinical article; treatment response; constipation; fatigue; cancer growth; diarrhea; drug efficacy; drug safety; hypertension; hypophosphatemia; risk benefit analysis; side effect; cancer patient; antigen expression; cancer immunotherapy; multiple cycle treatment; neutrophil count; anemia; nausea; vomiting; inflammation; bone pain; acute lymphoblastic leukemia; pediatric; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; backache; coughing; dyspnea; febrile neutropenia; fever; gamma glutamyl transferase blood level; hyperglycemia; hypoxia; alanine aminotransferase; aspartate aminotransferase; drug fatality; hypoalbuminemia; hypokalemia; hyponatremia; hypotension; drug response; clinical evaluation; peripheral edema; limb pain; allogeneic hematopoietic stem cell transplantation; safety; anxiety; headache; maximum plasma concentration; drug blood level; leukocyte count; periorbital edema; childhood leukemia; gamma glutamyltransferase; hemolytic uremic syndrome; disease exacerbation; tachycardia; repeated drug dose; pharmacokinetics; plasma concentration-time curve; blurred vision; platelet count; hypocalcemia; sinus tachycardia; adult respiratory distress syndrome; cd22 antigen; phase 2 clinical trial (topic); phase 1 clinical trial (topic); face edema; emotional disorder; lung edema; capillary leak syndrome; drug disposition; vein occlusion; multicenter study (topic); tumor immunogenicity; body weight disorder; blinatumomab; moxetumomab pasudotox; plasma clearance; intention to treat analysis; human; male; female; priority journal; article; elimination half-life; body weight gain; pediatric patient; moxetumomab; cat-8015; relapsed refractory acute lymphoblastic leukemia
Journal Title: Pediatric Blood and Cancer
Volume: 67
Issue: 5
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2020-05-01
Start Page: e28112
Language: English
DOI: 10.1002/pbc.28112
PUBMED: 31944549
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 May 2020 -- Source: Scopus
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MSK Authors
  1. Tanya M Trippett
    110 Trippett