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A Phase II Trial of Hu14.18K322A in Combination with Induction Chemotherapy in Children with Newly Diagnosed High-Risk Neuroblastoma.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Nov 01; Vol. 25 (21), pp. 6320-6328. Date of Electronic Publication: 2019 Oct 10. - Publication Year :
- 2019
-
Abstract
- Purpose: We sought to evaluate whether combining a humanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma.<br />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 isotretinoin were then administered. Secondary outcomes included reduced tumor volume and semiquantitative <superscript>123</superscript> I-metaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction.<br />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).<br />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.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Adolescent
Adult
Antibodies, Monoclonal, Humanized adverse effects
Antineoplastic Combined Chemotherapy Protocols adverse effects
Child
Disease-Free Survival
Female
Gangliosides
Granulocyte-Macrophage Colony-Stimulating Factor adverse effects
Humans
Induction Chemotherapy adverse effects
Kaplan-Meier Estimate
Killer Cells, Natural drug effects
Male
Neuroblastoma pathology
Progression-Free Survival
Prospective Studies
Young Adult
Antibodies, Monoclonal, Humanized administration & dosage
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage
Neuroblastoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 25
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31601569
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-19-1452