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

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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 languageEnglish
Pages (from-to)6320-6328
Number of pages9
JournalClinical Cancer Research
Issue number21
StatePublished - Nov 1 2019

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2019 American Association for Cancer Research.

ASJC Scopus subject areas

  • Medicine (all)


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