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

NCT06438614 | Completed Phase 2 FDA Drug

• 1 other identifier: HSJD HR NB.2 2019
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Refractory Neuroblastoma; Soft Tissue Cancer

Outcome Measures

Primary Outcomes (9)

• Number of Participants with Serious and Non-Serious Adverse Events

  The safety and tolerability of the treatment will be determined by means of type, incidence, severity, timing, seriousness, and relatedness of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI CTCA E v 5 .0

  14 months after ICF signature

• Best Overall Response (at the end of HITS treatment)

  Best Overall Response is defined as the best response recorded from the start of the study treatment

  From first day of treatment with HITS until completion of HITS (39 days).

• Best Overall Response of Complete Response (CR) (at the end of HITS treatment)

  The number and proportion of patients with CR as Best Overall Response at the end of HITS treatment

  From first day of treatment with HITS until completion of HITS(39 days).

• Objective Response Rate (at the end of HITS treatment)

  Objective Response Rate is defined as the proportion of patients with Best Overall Response of CR (complete response) or PR (partial response).

  From first day of treatment with HITS until completion of HITS (39 days).

• Clinical Benefit Rate (at the end of HITS treatment)

  Clinical Benefit Rate is defined as the proportion of patients with Best Overall Response of CR (complete response) or PR (partial response) or SD (stable disease) ≥ 24 w

  From first day of treatment with HITS until completion of HITS (39 days).

• Best Overall Response (at the end of NICE treatment)

  Best Overall Response is defined as the best response recorded from the start of the study treatment

  From first day of treatment with NICE until completion of NICE (39 days).

• Best Overall Response of Complete Response (CR) (at the end of NICE treatment)

  The number and proportion of patients with CR as Best Overall Response at the end of NICE treatment

  From first day of treatment with NICE until completion of NICE (39 days).

• Objective Response Rate (at the end of NICE treatment)

  Objective Response Rate is defined as the proportion of patients with Best Overall Response of CR (complete response) or PR (partial response).

  From first day of treatment with NICE until completion of NICE (39 days).

• Clinical Benefit Rate (at the end of NICE treatment)

  Clinical Benefit Rate is defined as the proportion of patients with Best Overall Response of CR (complete response) or PR (partial response) or SD (stable disease) ≥ 24 w

  From first day of treatment with NICE until completion of NICE (39 days).

Secondary Outcomes (3)

• To evaluate serum cytokines in patients receiving NICE

  From first day of treatment with NICE, until day 11 post administration.

• To measure MRD after HITS

  From first day of treatment with HITS until completion of HITS (39 days).

• To measure MRD after NICE

  From first day of treatment with NICE until completion of NICE (39 days).

Study Arms (1)

Arm 1

EXPERIMENTAL

Treatment involves 2 cycles of HITS: hu3F8, irinotecan, temozolomide, and GM-CSF. Irinotecan and temozolomide are given for 5 days, and hu3F8 and GM-CSF on specific days. Following this, 5 cycles of Naxitamab + GM-CSF are administered. Patients without a response receive NICE: hu3F8, GM-CSF, carboplatin, ifosfamide, and etoposide for 4 cycles. Patients with a complete response (CR) move to Naxitamab consolidation (5 cycles). This involves GM-CSF before and after, and hu3F8 on days 1, 3, and 5. Those with less than CR undergo 2 more NICE cycles, evaluated after the 4th. Lack of response leads to removal from the study.

Drug: HITS; Drug: Naxitamab + GM-CSF cycles; Drug: NICE

Interventions

HITS DRUG

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

Arm 1

Naxitamab + GM-CSF cycles DRUG

Patients that achieve CR after 2 or 4 cycles of HITS will move on to 5 cycles of Naxitamab + GM-CSF cycles.

Arm 1

NICE DRUG

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

Arm 1

Eligibility Criteria

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

You may qualify if:

• Diagnosis of neuroblastoma (NB) as defined per INRC as
• histopathology of tumor biopsy, or
• BM aspirate or biopsy indicative of NB by histology plus high blood or urine catecholamine metabolite levels or MYCN amplification, or
• Fluorodeoxyglucose (FDG), MIBG avid lesion(s)
• High-risk NB as defined as any of the following:
• Stage 4 with MYCN amplification
• Stage 4 without MYC amplification \>1.5 y of age
• Stage 3 with MYCN amplification
• Relapsed/refractory Neuroblastoma with
• Evidence of soft tissue disease or
• Progessive disease/incomplete response/relapsed to previous treatment with Naxitamab plus GM-CSF
• Prior treatment with murine and hu3F8 is allowed
• Prior treatment with irinotecan or temozolomide or ICE is permitted
• Evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy
• Age ≥18 months

You may not qualify if:

• 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).
• Active life-threatening infection.
• Pregnant women or women who are breast-feeding.
• Inability to comply with protocol requirements, including genetic studies.
• History of allergy to GM-CSF ≥ G4 (Common Terminology Criteria for Adverse Events- CTCAE) or does not respond to treatment.
• Absolute Neutrophil Count (ANC) \< 500/uL .
• Platelet count \<50,000/uL.

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead

Study Sites (1)

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

MeSH Terms

Conditions

Neuroblastoma; Sarcoma

Interventions

naxitamab

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; Neoplasms, Connective and Soft Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: June 3, 2024
• Study Start: August 20, 2020
• Primary Completion: July 20, 2023
• Study Completion: October 24, 2023
• Last Updated: August 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)