A Phase 1 Study of Combotox in Pediatric Patients With Refractory B-lineage Acute Lymphoblastic Leukemia

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