A Phase II Single Center Study Of Naxitamab , Granulocyte Macrophage Colony Stimulating Factor (GM CSF and Ifosfamide Carboplatin Etoposide) For Patients With Relapsed Refractory , Soft Tissue or Anti GD2 Immunotherapy Refractory Neuroblastoma

HSJD HR NB.2 2019

The purpose of this study is to evaluate safety and efficacy of naxitamab, granulocyte macrophage Colony Stimulating Factor (GM CSF) and Isofosfamide/Carboplatin/Etoposide (NICE) for Patients With Relapsed /Refractory, soft tissue or anti GD2 immunotherapy refractory Neuroblastoma

2020-08-20

2023-07-20

2023-10-24

Completed

Early phase I

47

Inclusion Criteria: 1. Diagnosis of NB as defined per INRC as 1. histopathology of tumor biopsy, or 2. BM aspirate or biopsy indicative of NB by histology plus high blood or urine catecholamine metabolite levels or MYCN amplification, or 3. FDG, MIBG avid lesion(s) 2. High-risk NB as defined as any of the following: 1. Stage 4 with MYCN amplification 2. Stage 4 without MYC amplification \>1.5 y of age 3. Stage 3 with MYCN amplification 3. Relapsed/refractory Neuroblastoma with 1. Evidence of soft tissue disease or 2. Progessive disease/incomplete response/relapsed to previous treatment with Naxitamab plus GM-CSF 4. Prior treatment with murine and hu3F8 is allowed 5. Prior treatment with irinotecan or temozolomide or ICE is permitted 6. Evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy 7. Age ≥18 months 8. Acceptable hematological status defined as: 1. Hemoglobin ≥8 g/dL (5.0 mmol/L) 2. White blood cell count ≥1000/μL 3. ANC ≥500/μL 4. Platelet count ≥50,000/μL 9. Acceptable liver function defined as: 1. ALT and AST ≤5 times ULN 2. Bilirubin ≤1.5 x ULN 10. Acceptable kidney function defined as: a. eGFR \>60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation 11. Written informed consent from legal guardian(s) and/or patient in accordance with local regulations. Children must provide assent as required by local regulations (≥ 12 years old). Exclusion Criteria: 1. Existing major organ dysfunction \> grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets). 2. Active life-threatening infection. 3. Pregnant women or women who are breast-feeding. 4. Inability to comply with protocol requirements, including genetic studies. 5. History of allergy to GM-CSF ≥ G4 (CTCAE) or does not respond to treatment. 6. ANC \< 500/uL . 7. Platelet count \<50,000/uL. 8. Patients with relapsed/refractory Neuroblastoma with solely bone marrow/bone involvement. Only patients with B/BM compartiment disease who show progressive disease/incomplete response/relapsed to previous treatment with Naxitamab plus GM-CSF may be eligible (inclusion critèrium #3).

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Subjects will receive 2 cycles of HITS. Each cycle of HITS (4 doses of hu3F8, 5 doses of irinotecan and temozolomide and 5 doses of GM-CSF). Patients with CR after 2 or 4 cycles of HITS will receive 5 cycles of Naxitamab + GM-CSF cycles. Patients that do not have an objective response (CR/PR) will receive NICE within 3 weeks from last dose. Each cycle of NICE consists of 4 doses of hu3F8, 5 doses of GM-CSF, 1 dose of carboplatin, and 3 doses each of ifosfamide and etoposide. Patients with less than CR response (PR/SD) will receive 2 more cycles of NICE and evaluated after 4th cycle. Patients with no objective response at these timepoints will be removed from the study. Patients with CR will receive 5 cycles of Naxitamab consolidation cycles consisting of GM-CSF250mcg/m2/day SC administered from day -4 to day 0 and GM-CSF500mcg/m2/day SC administered from day 1 to day 5. Three doses of hu3F83 mg/kg IVwill be administrated, specifically on days 1, 3 and 5.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 47, 'type': 'ACTUAL'}}

2024-06-03