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Feasibility Study of a Novel Experimental Induction Protocol Combining B43-PAP (Anti-CD19) Immunotoxin With Standard Induction Chemotherapy in Children and Adolescents With Relapsed B-Lineage ALL

2015; Lippincott Williams & Wilkins; Volume: 38; Issue: 7 Linguagem: Inglês

10.1097/cji.0000000000000088

1537-4513

Holly J. Meany, Nita L. Seibel, Mark Krailo, Doojduen Villaluna, Zhengjia Chen, Paul S. Gaynon, Joseph P. Neglia, Julie R. Park, Raymond J. Hutchinson, Judith K. Sato, Robert J. Wells, William G. Woods, Gregory Reaman,

Neuroblastoma Research and Treatments

Background: B43-pokeweed antiviral protein (B43-PAP) is a high-affinity anti-CD19 immunotoxin that is capable of causing apoptotic death in B-lineage leukemic cells with a drug-resistant phenotype. B43-PAP exhibited in vivo antileukemic activity in preclinical studies as well as on a single-agent phase I clinical trial. This pediatric phase I/II study evaluated the toxicity profile and efficacy of B43-PAP immunotoxin in combination with standard induction chemotherapy in children and adolescents with relapsed CD19-positive B-lineage acute lymphoblastic leukemia (B-ALL). Pharmacokinetic profile and immunogenicity of B43-PAP were assessed. Experimental Design: B43-PAP in combination with standard 3 and 4-drug induction chemotherapy was administered on days 9–13 and 21–25 of a 28-day treatment course with vincristine, prednisone, L-asparaginase, daunomycin, and intrathecal methotrexate. Thirty patients with relapsed B-ALL were enrolled on study CCG-0957. Results: Grade III/IV nonhematologic dose-limiting toxicities were encountered in 4 patients evaluable for toxicity and included myalgias, motor dysfunction, pulmonary toxicity, and elevated liver transaminase. Dose-limiting toxicities occurred only with the 4-drug regimen. Fourteen patients achieved a complete remission at the end of induction among the 20 patients evaluable for response. Conclusions: B43-PAP in combination with standard induction chemotherapy can be safely administered and exhibits clinical antileukemic activity against relapsed B-ALL.