A phase 1 study of Combotox in pediatric patients with refractory B-lineage acute lymphoblastic leukemia

J Pediatr Hematol Oncol. 2009 Dec;31(12):936-41. doi: 10.1097/MPH.0b013e3181bdf211.


Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Combotox is a 1:1 mixture of RFB4-dgA and HD37-dgA which are immunotoxins that target the CD22 and CD19 antigens, respectively. Combotox has different toxicities and targets than chemotherapy and is, thus, a new candidate for the treatment of patients with relapsed ALL. Preclinical data have demonstrated which Combotox is effective in killing pre-B-ALL cell lines and cells from patients with pre-B ALL.

Methods: We designed and conducted a Phase 1 dose-escalation study using Combotox in children with refractory or relapsed B-lineage-ALL. Seventeen patients aged 1 to 16 years were enrolled in this multi-institution study. They were treated at 4-dose levels: 2 mg/m2, 4 mg/m2, 5 mg/m2, and 6 mg/m2.

Results: The maximum tolerated dose was 5 mg/m2 and graft versus host disease defined the maximum tolerated dose. Three patients experienced complete remission. Six additional patients experienced a decrease of >95% in their peripheral blood blast counts, and 1 patient experienced a decrease of 75%.

Conclusions: Combotox can be safely administered to children with refractory leukemia. It has clinically important anticancer activity as a single agent. The recommended dose for future studies is 5 mg/m2/dose.

Publication types

  • Case Reports
  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD19 / immunology
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunotoxins / therapeutic use*
  • Infant
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Ricin / therapeutic use*
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antigens, CD19
  • CD22 protein, human
  • Immunotoxins
  • Sialic Acid Binding Ig-like Lectin 2
  • Ricin