Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission.

NCT04909515 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 202
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 9

Brief Summary

This is a single-arm, uncontrolled, international, multi-center, clinical,phase 2 trial, in patients ≥ 12 months of age with high-risk neuroblastoma in first remission. 120 patients will be enrolled to receive naxitamab + GM-CSF in combination with isotretinoin.

Conditions

Neuroblastoma

Keywords

antibody; neuroblastoma; pediatric; naxitamab; first remission

Outcome Measures

Primary Outcomes (1)

• 2-year progression free survival (PFS)

  2-year PFS defined as the proportion of patients alive and without progressive disease (PD) or relapse 2 years after enrollment

  2 years

Secondary Outcomes (6)

• Progression free survival

  128 weeks

• 1-year progression free survival

  1 year

• 1-year and 2-year overall survival

  2 years

• 2-year event-free survival

  2 years

• Proportion of positive to negative minimal residual disease (MRD) after 2 cycles

  6 weeks

Study Arms (1)

naxitamab + GM-CSF + isotretinoin

EXPERIMENTAL

8 cycles. Cycles 1+2 naxitamab + GM-CSF, cycles 3-5 naxitamab + GM-CSF + isotretinoin, cycles 6-8 isotretinoin

Drug: Naxitamab; Drug: GM-CSF; Drug: Isotretinoin

Interventions

Naxitamab DRUG

3.0 mg/kg/day = 9.0 mg/kg/cycle

naxitamab + GM-CSF + isotretinoin

GM-CSF DRUG

250 - 500 microgram/m2/day

naxitamab + GM-CSF + isotretinoin

Isotretinoin DRUG

160 mg/m2/day

naxitamab + GM-CSF + isotretinoin

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentet neuroblastoma at time of diagnosis defined as
• Histopathology of solid tumor biopsy, or
• Bone marrow aspirate or biopsy indicative of neuroblastoma plus high blood or urine catecholamine metabolite levels
• Documented high-risk disease at time of initial diagnosis defined as
• MYNC-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
• Patient must have completed frontline therapy, and achieved one of the following:
• verified complete response according to INRC (bone marrow positive minimal residual disease is allowed as assessed by RTqPCR at site) after completion of induction and consolidation with or without autologous stem cell transplantation
• Verified partial response according to INRC for primary site and soft tissue, bone, and bone marrow metastases at pre-autologous stem cell transplantation evaluation (i.e., myeloablative chemotherapy + autologous stem cell transplantation required as part of frontline regimen). Furthermore, bone marrow response must be with ≤ 5% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy and bone response must be with ≤ 3 areas of abnormal uptake on 123I-MIBG scintigraphy
• Age ≥ 12 months at trial enrollment

You may not qualify if:

• Verified progressive disease during induction or consolidation therapy
• Any systemic anti-cancer therapy, including chemotherapy, within 3 weeks prior to enrollment
• Autologous stem cell transplantation within 6 weeks prior to enrollment or ongoing toxicity caused by the autologous stem cell transplantation 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)

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (9)

Hong Kong Children's Hospital

Kowloon, Hong Kong

Location

National Medical Research Center Pediatric Hematology, Oncology and Immunology n.a Dmitry Rogachev

Moscow, Russia

Location

Research Institute of Pediatric Oncology ad Hematology of N.N. Blokhin National Medical Research Center of Oncology

Moscow, Russia

Location

Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic

Saint Petersburg, Russia

Location

ICON Cancer Centre Novena

Singapore, Singapore

Location

KK Women's and Children's Hospital

Singapore, Singapore

Location

Asan Medical Center Childrens Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Soeul, South Korea

Location

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

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 1, 2021
• Study Start: December 2, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 1, 2022

Record last verified: 2022-08

Locations

HK (1); KR (3); SG (2); RU (3)