Naxitamab and GM-CSF in Combination With IT in Patients With High-Risk Neuroblastoma

NCT04560166 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 203
• Study Type: interventional
• Target: 2
• Locations: 2 countries
• Sites: 3

Brief Summary

An International, Single-Arm, Multicenter Phase 2 Trial.

Conditions

Neuroblastoma Recurrent

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC)

  84 days

Study Arms (1)

Naxitamab and GM-CSF in combination with irinotecan and temozolomide

EXPERIMENTAL

A treatment cycle is 21 days. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). Patients will receive up to 18 IT cycles after enrollment. Naxitamab and GM-CSF will be given for at least 8 cycles.

Drug: Naxitamab and GM-CSF in combination with irinotecan and temozolomide

Interventions

Naxitamab and GM-CSF in combination with irinotecan and temozolomide DRUG

* Irinotecan, solution for infusion (20 mg/mL) * Temozolomide, capsules (5 mg, 20 mg and 100 mg) * The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL) * Sargramostim (GM-CSF), lyophilized 250 µg single use vial (250 µg/vial)

Naxitamab and GM-CSF in combination with irinotecan and temozolomide

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:

• Neuroblastoma (NB)
• Documented high-risk disease
• Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids)
• Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following:
• verified first progression during multi-drug frontline treatment or
• verified first episode of relapse, defined as recurrence after response to frontline treatment, or
• verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score ≥3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above
• The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment:
• Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan
• MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction
• Age ≥ 12 months at enrollment
• Written informed consent

You may not qualify if:

• Myelodysplastic syndrome or any malignancy other than NB
• Any systemic anti-cancer therapy within 3 weeks
• Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator
• Therapeutic 131I-MIBG within 6 weeks prior to enrollment
• Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response
• Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment
• Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD
• NB in Bone Marrow (BM) only
• NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment
• Performance status of \< 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older)
• Life expectancy of less than 6 months
• Left ventricular ejection fraction \< 50% by echocardiography
• Inadequate pulmonary function
• Diarrhea Grade ≥ 2
• 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

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (3)

Hong Kong Children's Hospital

Hong Kong, Hong Kong

Location

Asan Medical Center Children's Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Interventions

naxitamab; Granulocyte-Macrophage Colony-Stimulating Factor; Irinotecan; Temozolomide

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; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Terminated due to business priorities resulting from slow recruitment.

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Y-mAbs Therapeutics

clinicaltrials@ymabs.com

+4570261414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 23, 2020
• Study Start: November 8, 2021
• Primary Completion: September 21, 2022
• Study Completion: September 21, 2022
• Last Updated: March 18, 2024
• Results First Posted: March 18, 2024

Record last verified: 2024-02

Locations

HK (1); KR (2)