Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Combined With Isotretinoin for Maintenance Treatment of Patients With High-Risk Neuroblastoma in First Complete Response.

NCT06047535 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: ONN203
• Study Type: interventional
• Target: 62
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, multicenter clinical trial conducted in patients ≥ 12 months of age with high-risk neuroblastoma in first complete response. 62 patients will be enrolled to receive naxitamab + GM-CSF in combination with isotretinoin. In line with post-consolidation maintenance treatment of high-risk neuroblastoma, this trial will include patients with high-risk neuroblastoma in first complete response. Patients must have completed a multimodal frontline regimen (induction and consolidation) and have achieved complete response (positive bone marrow minimal residual disease as assessed by RTqPCR is allowed) following the multi agent induction and consolidation therapy.

Conditions

Neuroblastoma

Keywords

high-risk neuroblastoma with first complete response

Outcome Measures

Primary Outcomes (1)

• 2-year progression free survival

  2-year progression free survival defined as the proportion of patients alive and without progressive disease or relapse 2 years after enrollment

  2 years

Interventions

Naxitamab DRUG

Naxitamab + GM-CSF: Cycles 1-5: Patients will receive naxitamab IV at 3 mg/kg/infusion on Day 1, 3 and 5 and GM-CSF sc at 5 µg/kg/day on Days -4 to 0 and at 10 µg/kg/day on Days 1-5 for 5 cycles. Isotretinoin: Cycles 3-8: Patients will receive isotretinoin PO at 160 mg/m2/day divided into two daily doses on Days 15-28 for 6 cycles.

Also known as: GM-CSF, isotretinoin

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented NB at time of diagnosis defined as26:
• histopathology of solid tumor biopsy, or
• BM aspirate or biopsy indicative of NB plus high blood or urine catecholamine metabolite levels
• Documented high-risk disease at time of initial diagnosis defined as24, 26:
• MYCN-amplified at stage L2, M or MS (according to International Neuroblastoma Risk Group (INRG)) of any age or
• MYCN-nonamplified with stage M (according to INRG) and diagnosed at ≥ 18 months of age or
• Subjects must have completed frontline therapy described in 6.3.2 and have verified complete response according to INRC25 (BM MRD is allowed as assessed by RTqPCR at site28) after completion of induction and consolidation with or without ASCT
• Age ≥ 12 months at trial enrollment
• Life expectancy of greater than 6 months, as judged by the Investigator
• Written informed consent from legal guardian(s) and/or patient in accordance with local regulations. Children must provide assent as required by local regulations

You may not qualify if:

• Verified PD during induction or consolidation therapy
• Any systemic anti-cancer therapy, including chemotherapy, within 3 weeks prior to enrollment
• ASCT within 6 weeks prior to enrollment or ongoing toxicity caused by the ASCT at the discretion of the Investigator
• Therapeutic 131I-MIBG within 6 weeks prior to enrollment
• Prior anti-GD2 therapy
• Performance status of \< 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (patients aged 16 years or older)
• Left ventricular ejection fraction \< 50% by echocardiography
• Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry \< 94% and/or abnormal pulmonary function tests if these assessments are necessary at the discretion of the Investigator
• Life threatening infection(s)
• Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF
• Treatment with immunosuppressive agents (local steroids excluded) within 4 weeks prior to enrollment
• History of allergy or known hypersensitivity to GM-CSF, E. coli-derived products, or any component of GM-CSF, naxitamab, isotretinoin or vitamin A.
• NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment
• Patients with uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment)
• Unacceptable hematological status prior to first dosing, defined as one of the following:

Sponsors & Collaborators

• SciClone Pharmaceuticals: lead

MeSH Terms

Conditions

Neuroblastoma

Interventions

naxitamab; Granulocyte-Macrophage Colony-Stimulating Factor; Isotretinoin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 21, 2023
• Study Start: October 31, 2023
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): August 15, 2027
• Last Updated: September 21, 2023

Record last verified: 2023-09