Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia.
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.
Pediatric blood & cancer
Adolescent; Bacterial Toxins; Biomarkers, Tumor; Child; Child, Preschool; Exotoxins; Female; Humans; Infant; Male; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
CAT-8015; moxetumomab; pediatric; pharmacokinetics; safety
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., Pastan, I., Wayne, A. S. Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia. Pediatric blood & cancer 67, (2020).