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

• Sponsor: Y-mAbs Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04909515
• Collaborator: (none)
• Enrollment: 120
• Locations: 9
• Arm: 1
• Anticipated Duration (Months): 63.9
• Patients Per Site: 13.3
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Drug: Naxitamab; Drug: GM-CSF; Drug: Isotretinoin	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 2, 2021
• Anticipated Primary Completion Date: Jun 1, 2026
• Anticipated Study Completion Date: Apr 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 2-year progression free survival (PFS) [2 years]

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

Secondary Outcome Measures

1. Progression free survival [128 weeks]

   Progression free survival (defined as time from enrollment until progressive disease/relapse or death, whichever comes first)

2. 1-year progression free survival [1 year]

   1-year progression free survival defined as the proportion of patients alive and without progressive disease or relapse 1 year after enrollment

3. 1-year and 2-year overall survival [2 years]

   1-year and 2-year overall survival defined as the proportion of patients alive 1 year and 2 years after enrollment, respectively

4. 2-year event-free survival [2 years]

   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

5. Proportion of positive to negative minimal residual disease (MRD) after 2 cycles [6 weeks]

   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. Proportion of patients with MD positive convert to MRD negative [6 weeks]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Documentet neuroblastoma at time of diagnosis defined as

2. Histopathology of solid tumor biopsy, or

3. Bone marrow aspirate or biopsy indicative of neuroblastoma plus high blood or urine catecholamine metabolite levels

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

5. MYNC-amplified at stage L2, M or MS (according to International Neuroblastoma Risk Group (INRG)) of any age or

6. MYCN-nonamplified with stage M (according to INRG) and diagnosed at ≥ 18 months of age or

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

8. 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

9. 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

10. 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hong Kong Children's Hospital	Kowloon		Hong Kong
2	Asan Medical Center Childrens Hospital	Seoul		Korea, Republic of
3	Samsung Medical Center	Seoul		Korea, Republic of
4	Seoul National University Hospital	Soeul		Korea, Republic of
5	National Medical Research Center Pediatric Hematology, Oncology and Immunology n.a Dmitry Rogachev	Moscow		Russian Federation
6	Research Institute of Pediatric Oncology ad Hematology of N.N. Blokhin National Medical Research Center of Oncology	Moscow		Russian Federation
7	Raisa Gorbacheva Memorial Institute of Children Hematology and Transplantation Bone marrow Transplant Clinic	Saint Petersburg		Russian Federation
8	ICON Cancer Centre Novena	Singapore		Singapore
9	KK Women's and Children's Hospital	Singapore		Singapore

Sponsors and Collaborators

• Y-mAbs Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Y-mAbs Therapeutics
• ClinicalTrials.gov Identifier: NCT04909515
• Other Study ID Numbers: 202
• First Posted: Jun 1, 2021
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Y-mAbs Therapeutics: antibody; neuroblastoma; pediatric; naxitamab; first remission
• Additional relevant MeSH terms: Neuroblastoma; Isotretinoin

Study Results

No Results Posted as of Feb 1, 2022