NCT06438614

A Study Of Naxitamab , Granulocyte Macrophage Colony Stimulating Factor For Patients With Relapsed /Refractory , Soft Tissue or Anti GD2 Immunotherapy Refractory Neuroblastoma

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Fundació Sant Joan de Déu · Academic / Other
• Sex: All
• Age: 18 Months
• Healthy volunteers: Not accepted

Summary

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

Detailed description

The anti-GD2 monoclonal antibody Naxitamab (also known as hu3F8) in combination with macrophage colony-stimulating factor (GM-CSF) is currently under pivotal phase 3 investigation for the treatment of High-Risk Neuroblastoma Patients with Primary or Secondary Refractory Osteomedullary Disease. A subset of patients with high-risk, resistant disease, i.e., relapsed or refractory Neuroblastoma with soft tissue involvement as measured by 123I-Meta-iodobenzylguanidine (MIBG), 18F-FDG avid or measurable computed tomography (CT)/ magnetic resonance imaging (MRI) tumors outside of the bone marrow, or disease refractory to Naxitamab in combination with GM-CSF has shown significant response rates to a chemoimmunotherapy combination of Naxitamab, GM-CSF, irinotecan and temozolomide (HITS- Hu3F8, irinotecan, temozolomide and sargramostim) (NCT03189706). Treatment is administered on an outpatient basis and toxicities include those expected from I/T (myelosuppression and diarrhea) as well as pain and hypertension expected with Naxitamab. No other greater than grade 2 related toxicities occurred in this study (n=46). Early responses, assessed after 2 cycles, were documented in 18 (39%) patients and here complete (n = 9), partial (n = 8), and mixed (n = 1) and 13 patients had stable disease. Responses were achieved in refractory (3/7;43%) and progressive disease (15/39;38%) subgroups, in patients who had previously received I/T (12/34;35%) and/or anti-GD2 MoAb (14/36;39%), and in soft tissue (6/22; 27%) MIBG-avid skeletal sites (20/36;56%) and on bone marrow histology (9/12;75%). While encouraging, new strategies are warranted to further treat resistant disease. A high-dose combination of ifosfamide, carboplatin, and etoposide (ICE) has activity against Neuroblastoma without cross-resistance to widely used chemotherapy regimens. Through compassionate use, 4 patients with progression of disease or refractory disease after HITS therapy, have been further treated with two cycles of a combination of naxitamab, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and ifosfamide/Carboplatin/Etoposide (NICE). The first patient showed a complete response. Toxicity included G2 prolonged aplasia and G3 hypertension, both expected from the chemotherapy agents and hu3F8. One patient progressed after the 2 cycles and the other 2 showed stable disease, according to the revised (2017) International Neuroblastoma Response Criteria (INRC). In this formal trial, the investigators will investigate whether the combination of Naxitamab and GM-CSF with ifosfamide/Carboplatin/Etoposide (ICE) has a synergistic treatment effect in relapsed or refractory disease. The safety and efficacy of NICE (Naxitamab, Ifosfamide/Carboplatin/Etoposide) in patients that have not achieved complete remission with HITS chemo-immunotherapy will be assessed.

Conditions

• Refractory Neuroblastoma
• Soft Tissue Cancer

Interventions

Type	Name	Description
DRUG	HITS	Four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF. Irinotecan 50mg/m2/day IV will be administered from day 1-5concurrently with temozolomide 150mg/m2/day orally. Hu3F8 2.25mg/kg IV will be administered on days 2, 4, 9and11. GM-CSF 250mcg/m2/day SC will be administered on days 7-11
DRUG	Naxitamab + GM-CSF cycles	Patients that achieve CR after 2 or 4 cycles of HITS will move on to 5 cycles of Naxitamab + GM-CSF cycles.
DRUG	NICE	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 four doses of hu3F8, five doses of GM-CSF, one dose of carboplatin, and 3 doses each of ifosfamide and etoposide (table 2). Hu3F8 2.25mg/kg IV will be administered on days 2, 4, 9and 11. GM-CSF 250mcg/m2/day SC will be administered on days 7-11. Ifosfamide 1.5 gr/m2/day IV will be administered from day 1-3 concurrently with etoposide 100 mg/m2/day IV. Carboplatin 400 mg/m2/day IV will be administered on day 1

Timeline

• Start date: 2020-08-20
• Primary completion: 2023-07-20
• Completion: 2023-10-24
• First posted: 2024-06-03
• Last updated: 2024-08-29

Locations

1 site across 1 country: Spain

Regulatory

• FDA-regulated drug study