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

TitleA Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma
Authors
Issue Date2019
Citation
Clinical Cancer Research, 2019, v. 25, n. 21, p. 6320-6328 How to Cite?
Abstract© 2019 American Association for Cancer Research. 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.
Persistent Identifierhttp://hdl.handle.net/10722/294530
ISSN
2020 Impact Factor: 12.531
2020 SCImago Journal Rankings: 5.427
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFurman, Wayne L.-
dc.contributor.authorFederico, Sara M.-
dc.contributor.authorMcCarville, Mary Beth-
dc.contributor.authorShulkin, Barry L.-
dc.contributor.authorDavidoff, Andrew M.-
dc.contributor.authorKrasin, Matthew J.-
dc.contributor.authorSahr, Natasha-
dc.contributor.authorSykes, April-
dc.contributor.authorWu, Jianrong-
dc.contributor.authorBrennan, Rachel C.-
dc.contributor.authorBishop, Michael William-
dc.contributor.authorHelmig, Sara-
dc.contributor.authorStewart, Elizabeth-
dc.contributor.authorNavid, Fariba-
dc.contributor.authorTriplett, Brandon-
dc.contributor.authorSantana, Victor M.-
dc.contributor.authorBahrami, Armita-
dc.contributor.authorAnthony, Gwendolyn-
dc.contributor.authorYu, Alice L.-
dc.contributor.authorHank, Jacquelyn-
dc.contributor.authorGillies, Stephen D.-
dc.contributor.authorSondel, Paul M.-
dc.contributor.authorLeung, Wing H.-
dc.contributor.authorPappo, Alberto S.-
dc.date.accessioned2020-12-03T08:22:56Z-
dc.date.available2020-12-03T08:22:56Z-
dc.date.issued2019-
dc.identifier.citationClinical Cancer Research, 2019, v. 25, n. 21, p. 6320-6328-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/294530-
dc.description.abstract© 2019 American Association for Cancer Research. 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.-
dc.languageeng-
dc.relation.ispartofClinical Cancer Research-
dc.titleA Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-19-1452-
dc.identifier.pmid31601569-
dc.identifier.pmcidPMC6825564-
dc.identifier.scopuseid_2-s2.0-85074446029-
dc.identifier.volume25-
dc.identifier.issue21-
dc.identifier.spage6320-
dc.identifier.epage6328-
dc.identifier.eissn1557-3265-
dc.identifier.isiWOS:000494399300007-
dc.identifier.issnl1078-0432-

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