Back to resultsNaxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission.
Primary Purpose
Neuroblastoma
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Naxitamab
GM-CSF
Isotretinoin
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring antibody, neuroblastoma, pediatric, naxitamab, first remission
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- 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)
Sites / Locations
- Hong Kong Children's Hospital
- Asan Medical Center Childrens Hospital
- Samsung Medical Center
- Seoul National University Hospital
- National Medical Research Center Pediatric Hematology, Oncology and Immunology n.a Dmitry Rogachev
- Research Institute of Pediatric Oncology ad Hematology of N.N. Blokhin National Medical Research Center of Oncology
- Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic
- ICON Cancer Centre Novena
- KK Women's and Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
naxitamab + GM-CSF + isotretinoin
Arm Description
8 cycles. Cycles 1+2 naxitamab + GM-CSF, cycles 3-5 naxitamab + GM-CSF + isotretinoin, cycles 6-8 isotretinoin
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Progression free survival
Progression free survival (defined as time from enrollment until progressive disease/relapse or death, whichever comes first)
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 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-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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04909515
Brief Title
Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission.
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study terminated due to business priorities
Study Start Date
December 2, 2021 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
April 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Y-mAbs Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
antibody, neuroblastoma, pediatric, naxitamab, first remission
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
naxitamab + GM-CSF + isotretinoin
Arm Type
Experimental
Arm Description
8 cycles. Cycles 1+2 naxitamab + GM-CSF, cycles 3-5 naxitamab + GM-CSF + isotretinoin, cycles 6-8 isotretinoin
Intervention Type
Drug
Intervention Name(s)
Naxitamab
Intervention Description
3.0 mg/kg/day = 9.0 mg/kg/cycle
Intervention Type
Drug
Intervention Name(s)
GM-CSF
Intervention Description
250 - 500 microgram/m2/day
Intervention Type
Drug
Intervention Name(s)
Isotretinoin
Intervention Description
160 mg/m2/day
Primary Outcome Measure Information:
Title
2-year progression free survival (PFS)
Description
2-year PFS defined as the proportion of patients alive and without progressive disease (PD) or relapse 2 years after enrollment
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival (defined as time from enrollment until progressive disease/relapse or death, whichever comes first)
Time Frame
128 weeks
Title
1-year progression free survival
Description
1-year progression free survival defined as the proportion of patients alive and without progressive disease or relapse 1 year after enrollment
Time Frame
1 year
Title
1-year and 2-year overall survival
Description
1-year and 2-year overall survival defined as the proportion of patients alive 1 year and 2 years after enrollment, respectively
Time Frame
2 years
Title
2-year event-free survival
Description
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
Time Frame
2 years
Title
Proportion of positive to negative minimal residual disease (MRD) after 2 cycles
Description
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
Time Frame
6 weeks
Title
Proportion of patients with MD positive convert to MRD negative
Description
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
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
Facility Information:
Facility Name
Hong Kong Children's Hospital
City
Kowloon
Country
Hong Kong
Facility Name
Asan Medical Center Childrens Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Soeul
Country
Korea, Republic of
Facility Name
National Medical Research Center Pediatric Hematology, Oncology and Immunology n.a Dmitry Rogachev
City
Moscow
Country
Russian Federation
Facility Name
Research Institute of Pediatric Oncology ad Hematology of N.N. Blokhin National Medical Research Center of Oncology
City
Moscow
Country
Russian Federation
Facility Name
Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic
City
Saint Petersburg
Country
Russian Federation
Facility Name
ICON Cancer Centre Novena
City
Singapore
Country
Singapore
Facility Name
KK Women's and Children's Hospital
City
Singapore
Country
Singapore
12. IPD Sharing Statement
Learn more about this trial
Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor (GMCSF) and Isotretinoin for Consolidation of Patients With High-Risk Neuroblastoma in First Remission.
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