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

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04909515
• Other study ID #: 202
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2, 2021
• Est. completion date: April 2027

Study information

• Verified date: August 2022
• Source: Y-mAbs Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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)

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• Naxitamab
3.0 mg/kg/day = 9.0 mg/kg/cycle
• GM-CSF
250 - 500 microgram/m2/day
• Isotretinoin
160 mg/m2/day

Locations

Country	Name	City	State
Hong Kong	Hong Kong Children's Hospital	Kowloon
Korea, Republic of	Asan Medical Center Childrens Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Soeul
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	Moscow
Russian Federation	Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic	Saint Petersburg
Singapore	ICON Cancer Centre Novena	Singapore
Singapore	KK Women's and Children's Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Y-mAbs Therapeutics

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Russian Federation,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival	Progression free survival (defined as time from enrollment until progressive disease/relapse or death, whichever comes first)	128 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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