A clinical study in which High-Risk Neuroblastoma Patients with Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow are treated with Antibody Naxitamab (hu3F8) (study drug) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The tolerability and efficacy of the drug will be tested.

Phase 1

Conditions: Treatment of high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/orbone marrow
MedDRA version: 21.0Level: PTClassification code 10066595Term: Neuroblastoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-001829-40-GB

Lead Sponsor: Y-mAbs Therapeutics A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 95

Inclusion Criteria

1. Documented diagnosis of neuroblastoma (NB) as defined per INRC as
a. histopathology of tumor biopsy, or
b. Bone marrow (BM) aspirate or biopsy indicative of NB by histology,
plus high blood or urine catecholamine metabolite levels or
Myelocytomatosis Viral-Related Oncogene, Neuroblastoma derived
(MYCN) amplification, or
c. MIBG-avid lesion(s)
2. High-risk NB with either primary refractory or secondary refractory
disease or
incomplete response to salvage treatment (in both cases including SD,
MR and PR) evaluable in bone and/or BM as defined in section 6.7. If
disease is only present in bone the patient must have evaluable disease
outside the radiation areas for being eligible in the trial, please see
section 7.2.1. If disease is only present in the BM the involvement must
be >5%.
3. Life expectancy =6 months
4. Age =12 months
5. Acceptable hematological status, (hematological support is allowed if administered =1 week before first infusion of naxitamab), defined as:
a. Hemoglobin =8 g/dL (5.0 mmol/L)
b. White blood cell count =1000/µL
c. Absolute neutrophil count (ANC) =500/µL
d. Platelet count =25,000/µL
6. Acceptable liver function defined as:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) =5 times upper limit of normal (ULN)
b. Bilirubin =1.5 x ULN
7. Acceptable kidney function defined as:
a. Estimated Glomerular Filtration Rate (eGFR) >60 mL/min/1.73 m2
calculated by the 2009 revised Bedside Schwartz Equation
8. Written informed consent from legal guardian(s) and/or patient in
accordance with local regulations. Children must provide assent as
required by local regulations.

Are the trial subjects under 18? yes
Number of subjects for this age range: 95
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks of 1st dose of GM-CSF
2. Evaluable NB outside bone and BM defined as follows:
• MIBG-avid tumor: Definite MIBG uptake in tumor tissues outside bone
and BM
• MIBG nonavid tumor: Definite uptake in tumor tissues outside bone
and BM on FDG-PET
3. Actively Progressive Disease at trial entry
4. Existing major organ dysfunction CTCAE >Grade 2, with the exception of hearing loss, hematological status, kidney and liver function.
5. Active life-threatening infection
6. Prior treatment with naxitamab
7. Karnofsky/Lansky score <50%
8. Pregnancy or a woman who is breast-feeding (women of child-bearing
potential must have a negative pregnancy test at screening). A woman of child-bearing potential is excluded if she does not agree to use highly effective contraception for a period of 40 days after the last naxitamab infusion section 9.2.5 in protocol. A sterilized or infertile woman is exempt from the requirement to use contraception after hu3F8 treatment: she must have undergone surgical sterilization
(hysterectomy, or bilateral ovariectomy)
9. Inability to comply with protocol requirements, including PK studies,
as determined by the investigator
10. History of allergy or known hypersensitivity to GM-CSF, yeast derived
products, or any component of the GM-CSF or naxitamab
11. History of anaphylactic reactions CTCAE grade 4 related to prior GD2 antibody therapy.
12. NB in central nervous system (CNS) within 6 months of 1st dose of GM-CSF
13. Prior treatment with omburtamab (mu8H9) within 6 months of 1st dose of GM-CSF
14. Patients who have had allogeneic hematopoietic stem cell
transplantation (allo-SCT) or donor-lymphocyte-infusion (DLI). DLI or
buffy coat infusion is defined as any kind of active allogenic lymphocyte
suspension
a. within 6 months of 1st dose of GM-CSF or
b. with a lymphocyte count < 0.2 x109/L
15. Patients who received Hematopoietic Progenitor Cell (HPC) boost or
top-up of allogenic stem cells (lymphocyte-depleted) within 2 months
of 1st dose GM-CSF.
16. Any clinically meaningful abnormal finding in physical examination,
vital signs, ECG, hematology, clinical chemistry, or urinalysis prior to
inclusion into the trial, which in the opinion of the investigator, may put
the subject at risk because of his/her participation in the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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