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

Larry Herrera, Bruce Bostrom, Lisa Gore, Eric Sandler, Glen Lew, Paul G. Schlegel, Victor Aquino, Victor Ghetie, Ellen S. Vitetta, John Schindler

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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: 2mg/m, 4mg/m, 5mg/m, and 6mg/m. Results: The maximum tolerated dose was 5mg/m 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 5mg/m/dose.

Original languageEnglish (US)
Pages (from-to)936-941
Number of pages6
JournalJournal of Pediatric Hematology/Oncology
Issue number12
StatePublished - Dec 1 2009


  • Immunotoxins
  • Pediatric acute lymphoblastic leukemia

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology


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