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: A report from the children's oncology group

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

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Abstract

Background: B43-pokeweed antiviral protein (B43-PAP) is a highaffinity 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.

Original languageEnglish (US)
Pages (from-to)299-305
Number of pages7
JournalJournal of Immunotherapy
Volume38
Issue number7
DOIs
StatePublished - Aug 1 2015

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Immunotoxins
Induction Chemotherapy
Feasibility Studies
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pharmaceutical Preparations
Asparaginase
Clinical Trials, Phase I
Daunorubicin
Myalgia
Vincristine
Prednisone
Transaminases
Methotrexate
pokeweed antiviral protein
Research Design
Pharmacokinetics
Pediatrics
Phenotype
Lung
Liver

Keywords

  • Anti-CD19 immunotoxin
  • Immunotherapy
  • Relapsed B-lineage ALL

Cite this

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 : A report from the children's oncology group. / Meany, Holly J.; Seibel, Nita L.; Krailo, Mark; Villaluna, Doojduen; Chen, Zhengjia; Gaynon, Paul; Neglia, Joseph P.; Park, Julie R.; Hutchinson, Raymond; Sato, Judith K.; Wells, Robert J.; Woods, William G.; Reaman, Gregory.

In: Journal of Immunotherapy, Vol. 38, No. 7, 01.08.2015, p. 299-305.

Research output: Contribution to journalArticle

Meany, Holly J. ; Seibel, Nita L. ; Krailo, Mark ; Villaluna, Doojduen ; Chen, Zhengjia ; Gaynon, Paul ; Neglia, Joseph P. ; Park, Julie R. ; Hutchinson, Raymond ; Sato, Judith K. ; Wells, Robert J. ; Woods, William G. ; Reaman, Gregory. / 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 : A report from the children's oncology group. In: Journal of Immunotherapy. 2015 ; Vol. 38, No. 7. pp. 299-305.
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abstract = "Background: B43-pokeweed antiviral protein (B43-PAP) is a highaffinity 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.",
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T1 - 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

T2 - A report from the children's oncology group

AU - Meany, Holly J.

AU - Seibel, Nita L.

AU - Krailo, Mark

AU - Villaluna, Doojduen

AU - Chen, Zhengjia

AU - Gaynon, Paul

AU - Neglia, Joseph P.

AU - Park, Julie R.

AU - Hutchinson, Raymond

AU - Sato, Judith K.

AU - Wells, Robert J.

AU - Woods, William G.

AU - Reaman, Gregory

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Background: B43-pokeweed antiviral protein (B43-PAP) is a highaffinity 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.

AB - Background: B43-pokeweed antiviral protein (B43-PAP) is a highaffinity 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.

KW - Anti-CD19 immunotoxin

KW - Immunotherapy

KW - Relapsed B-lineage ALL

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