Phase I trial of anti-B4-blocked ricin in pediatric patients with leukemia and lymphoma.

Monoclonal antibodies, specific for antigens expressed on lymphoid malignancies, which have been conjugated to toxins such as ricin, hold promise in the therapy of childhood leukemia and lymphoma. Anti-B4-blocked ricin (anti-B4-bR) is such an agent, and a phase I study of this agent was conducted in children with relapsed or refractory B-lineage leukemia and lymphoma. Anti-B4-bR was given as two 7-day continuous infusions separated by 7 days. Twenty patients were enrolled and 19 received the drug. Two dosage levels (30 and 40 microg/kg per day) were evaluated. Forty micrograms per kilogram per day was the maximally tolerated dose. Dose-limiting toxicity was capillary leak syndrome. Grade 3 reversible elevation in transaminases was also encountered. Human antimouse antibodies or human antiricin antibodies were detected in five patients. No complete remissions or partial remissions were seen.