A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma

Wayne L. Furman; Sara M. Federico; Mary Beth McCarville; Barry L. Shulkin; Andrew M. Davidoff; Matthew J. Krasin; Natasha Sahr; April Sykes; Jianrong Wu; Rachel C. Brennan; Michael William Bishop; Sara Helmig; Elizabeth Stewart; Fariba Navid; Brandon Triplett; Victor M. Santana; Armita Bahrami; Gwendolyn Anthony; Alice L. Yu; Jacquelyn Hank; Stephen D. Gillies; Paul M. Sondel; Wing H. Leung; Alberto S. Pappo

doi:10.1158/1078-0432.CCR-19-1452

A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma

Wayne L. Furman, Sara M. Federico, Mary Beth McCarville, Barry L. Shulkin, Andrew M. Davidoff, Matthew J. Krasin, Natasha Sahr, April Sykes, Jianrong Wu, Rachel C. Brennan, Michael William Bishop, Sara Helmig, Elizabeth Stewart, Fariba Navid, Brandon Triplett, Victor M. Santana, Armita Bahrami, Gwendolyn Anthony, Alice L. Yu, Jacquelyn HankStephen D. Gillies, Paul M. Sondel, Wing H. Leung, Alberto S. Pappo

Internal Medicine

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.

Original language	English
Pages (from-to)	6320-6328
Number of pages	9
Journal	Clinical Cancer Research
Volume	25
Issue number	21
DOIs	https://doi.org/10.1158/1078-0432.CCR-19-1452
State	Published - Nov 1 2019

Bibliographical note

Publisher Copyright:
© 2019 American Association for Cancer Research.

Funding

The authors thank Deanna Welsh for data management and Nisha Badders, PhD, ELS, for scientific editing. This study was supported by St. Jude Children's Research Hospital Comprehensive Cancer Center Support Grant (2 P30 CA021765), American Lebanese Syrian Associated Charities, and Cookies for Kids' Cancer and Cure Childhood Cancer Foundation.

Funders	Funder number
Cookies for Kids’ Cancer and Cure Childhood Cancer Foundation
National Childhood Cancer Registry – National Cancer Institute	P30CA021765
St. Jude Children's Research Hospital	2 P30 CA021765
American Lebanese Syrian Associated Charities

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-19-1452

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Furman, W. L., Federico, S. M., McCarville, M. B., Shulkin, B. L., Davidoff, A. M., Krasin, M. J., Sahr, N., Sykes, A., Wu, J., Brennan, R. C., Bishop, M. W., Helmig, S., Stewart, E., Navid, F., Triplett, B., Santana, V. M., Bahrami, A., Anthony, G., Yu, A. L., ... Pappo, A. S. (2019). A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma. Clinical Cancer Research, 25(21), 6320-6328. https://doi.org/10.1158/1078-0432.CCR-19-1452

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title = "A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma",

abstract = "Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.",

author = "Furman, {Wayne L.} and Federico, {Sara M.} and McCarville, {Mary Beth} and Shulkin, {Barry L.} and Davidoff, {Andrew M.} and Krasin, {Matthew J.} and Natasha Sahr and April Sykes and Jianrong Wu and Brennan, {Rachel C.} and Bishop, {Michael William} and Sara Helmig and Elizabeth Stewart and Fariba Navid and Brandon Triplett and Santana, {Victor M.} and Armita Bahrami and Gwendolyn Anthony and Yu, {Alice L.} and Jacquelyn Hank and Gillies, {Stephen D.} and Sondel, {Paul M.} and Leung, {Wing H.} and Pappo, {Alberto S.}",

note = "Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",

year = "2019",

month = nov,

day = "1",

doi = "10.1158/1078-0432.CCR-19-1452",

language = "English",

volume = "25",

pages = "6320--6328",

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Furman, WL, Federico, SM, McCarville, MB, Shulkin, BL, Davidoff, AM, Krasin, MJ, Sahr, N, Sykes, A, Wu, J, Brennan, RC, Bishop, MW, Helmig, S, Stewart, E, Navid, F, Triplett, B, Santana, VM, Bahrami, A, Anthony, G, Yu, AL, Hank, J, Gillies, SD, Sondel, PM, Leung, WH & Pappo, AS 2019, 'A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma', Clinical Cancer Research, vol. 25, no. 21, pp. 6320-6328. https://doi.org/10.1158/1078-0432.CCR-19-1452

TY - JOUR

T1 - A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma

AU - Furman, Wayne L.

AU - Federico, Sara M.

AU - McCarville, Mary Beth

AU - Shulkin, Barry L.

AU - Davidoff, Andrew M.

AU - Krasin, Matthew J.

AU - Sahr, Natasha

AU - Sykes, April

AU - Wu, Jianrong

AU - Brennan, Rachel C.

AU - Bishop, Michael William

AU - Helmig, Sara

AU - Stewart, Elizabeth

AU - Navid, Fariba

AU - Triplett, Brandon

AU - Santana, Victor M.

AU - Bahrami, Armita

AU - Anthony, Gwendolyn

AU - Yu, Alice L.

AU - Hank, Jacquelyn

AU - Gillies, Stephen D.

AU - Sondel, Paul M.

AU - Leung, Wing H.

AU - Pappo, Alberto S.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.

AB - Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.

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U2 - 10.1158/1078-0432.CCR-19-1452

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A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma

Abstract

Bibliographical note

Funding

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UN SDGs

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