Phase I Study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia

Alan S. Wayne, Nirali N. Shah, Deepa Bhojwani, Lewis B. Silverman, James A. Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J. Kreitman, Mark C. Lanasa and Ira Pastan

Key points

  • A phase I trial of the anti-CD22 immunotoxin moxetumomab pasudotox was conducted in children with acute lymphoblastic leukemia.

  • A 32% objective response rate was observed, including 11 composite complete responses (23%), five of which were minimal residual disease-negative.


Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles. Cohorts B and C received dexamethasone prophylaxis against capillary leak syndrome (CLS). The most common treatment-related adverse events were reversible weight gain, hepatic transaminase elevation, and hypoalbuminemia. Dose-limiting CLS occurred in two of four patients receiving 30 µg/kg QOD × 6 doses. Incorporation of dexamethasone prevented further dose-limiting CLS. Six of 14 patients receiving 50 µg/kg × 10 doses developed hemolytic uremic syndrome (HUS), thrombotic microangiopathy (TMA) or HUS-like events, exceeding the MTCD. Treatment expansion at 40 µg/kg × 10 doses (n = 11) exceeded the MTCD due to two HUS/TMA/HUS-like events. Dose level 6B (50 µg/kg × 6 doses) was the MTCD, selected as the recommended phase II dose. Among 47 evaluable patients, an objective response rate of 32% was observed, including eleven (23%) composite complete responses, five of which were minimal residual disease-negative by flow cytometry. Moxetumomab pasudotox showed a manageable safety profile and evidence of activity in relapsed or refractory childhood ALL.

  • Submitted February 22, 2017.
  • Accepted July 27, 2017.