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

Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission. An International, Open-Label,Uncontrolled, Single-Arm, Multicenter, Phase 2 Trial

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.

Study Overview

• Status: Withdrawn
• Conditions: Neuroblastoma
• Intervention / Treatment: Drug: Naxitamab; Drug: GM-CSF; Drug: Isotretinoin

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Kowloon, Hong Kong
    • Hong Kong Children's Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Asan Medical Center Childrens Hospital
  • Soeul, Korea, Republic of
    • Seoul National University Hospital
• Russian Federation
  • Moscow, Russian Federation
    • National Medical Research Center Pediatric Hematology, Oncology and Immunology n.a Dmitry Rogachev
  • Moscow, Russian Federation
    • Research Institute of Pediatric Oncology ad Hematology of N.N. Blokhin National Medical Research Center of Oncology
  • Saint Petersburg, Russian Federation
    • Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic
• Singapore
  • Singapore, Singapore
    • KK Women's and Children's Hospital
  • Singapore, Singapore
    • ICON Cancer Centre Novena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Documentet neuroblastoma at time of diagnosis defined as

   1. Histopathology of solid tumor biopsy, or
   2. Bone marrow aspirate or biopsy indicative of neuroblastoma plus high blood or urine catecholamine metabolite levels

2. Documented high-risk disease at time of initial diagnosis defined as

   1. MYNC-amplified at stage L2, M or MS (according to International Neuroblastoma Risk Group (INRG)) of any age or
   2. MYCN-nonamplified with stage M (according to INRG) and diagnosed at ≥ 18 months of age or

3. Patient must have completed frontline therapy, and achieved one of the following:

   1. 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
   2. 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
4. Age ≥ 12 months at trial enrollment

Exclusion Criteria:

1. Verified progressive disease during induction or consolidation therapy
2. Any systemic anti-cancer therapy, including chemotherapy, within 3 weeks prior to enrollment
3. 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
4. Therapeutic 131I-MIBG within 6 weeks prior to enrollment
5. Prior anti-GD2 therapy
6. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: naxitamab + GM-CSF + isotretinoin; 8 cycles. Cycles 1+2 naxitamab + GM-CSF, cycles 3-5 naxitamab + GM-CSF + isotretinoin, cycles 6-8 isotretinoin	Drug: Naxitamab; 3.0 mg/kg/day = 9.0 mg/kg/cycle; Drug: GM-CSF; 250 - 500 microgram/m2/day; Drug: Isotretinoin; 160 mg/m2/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival (defined as time from enrollment until progressive disease/relapse or death, whichever comes first)	128 weeks
1-year progression free survival	1-year progression free survival defined as the proportion of patients alive and without progressive disease or relapse 1 year after enrollment	1 year
1-year and 2-year overall survival	1-year and 2-year overall survival defined as the proportion of patients alive 1 year and 2 years after enrollment, respectively	2 years
2-year event-free survival	2-year event-free survival, defined as the proportion of patients alive and without progressive disease, relapse, secondary malignancy or until last contact if no event occurred, 2 years after enrollment	2 years
Proportion of positive to negative minimal residual disease (MRD) after 2 cycles	Proportion of patients changing from minimal residual disease positive in bone marrow at enrollment (defined as patients assessed as minimal residual disease positive by RTqPCR of bone marrow at enrollment) to minimal residual disease negative at completion of Cycle 2	6 weeks
Proportion of patients with MD positive convert to MRD negative	Proportion of patients with disease in bone marrow at enrollment (i.e., minimal disease according to INRC) and convert to minimal residual disease negative (assessed by RTqPCR) at completion of Cycle 2	6 weeks

Collaborators and Investigators

• Sponsor: Y-mAbs Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 2, 2021
• Primary Completion (ANTICIPATED): June 1, 2026
• Study Completion (ANTICIPATED): April 1, 2027

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: May 27, 2021
• First Posted (ACTUAL): June 1, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: pediatric; antibody; neuroblastoma; naxitamab; first remission
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: 202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No