Treatment of high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow MedDRA version: 21.0 Level: PT Classification code 10066595 Term: Neuroblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: naxitamab drug product
Product Code: Hu3F8
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: naxitamab
CAS Number: 1879925-92-4
Current Sponsor code: Hu3F8 drug substance
O
Sponsors
Y-mAbs Therapeutics A/S
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the centrally assessed objective response rate (ORR) to naxitamab + GM-CSF;Secondary Objective: 1. To evaluate the safety of naxitamab + GM-CSF 2. To evaluate Duration of Response (DoR) to naxitamab + GM-CSF 3. To evaluate the complete response (CR) rate with naxitamab + GMCSF 4. To evaluate the investigator assessed objective response rate to naxitamab + GM-CSF 5. To evaluate the pharmacokinetics (PK) of naxitamab 6. To investigate the formation of Anti-Drug antibodies (ADAs) 7. To evaluate the safety of naxitamab + GM-CSF in patients with positive ADA at trial entry Secondary objectives in long-term follow-up: 8. To evaluate Progression-Free Survival (PFS) with naxitamab + GMCSF 9. To evaluate overall survival (OS) with naxitamab + GM-CSF;Primary end point(s): 1. Objective Response Rate (ORR), during the naxitamab treatment period, centrally assessed according to the International Neuroblastoma Response Criteria (INRC);Timepoint(s) of evaluation of this end point: During and up to 101 weeks following the first naxitamab treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety will be evaluated by the incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. 2. DoR, defined as the time from first objective response [CR or partial response (PR)] to PD; data will be censored at the date of last disease evaluation before new anti-NB treatment 3. Complete response rate, during the naxitamab treatment period, centrally assessed according to the INRC 4. ORR, during the naxitamab treatment period, investigator assessed according to the International Neuroblastoma Response Criteria (INRC) 5. Assessment of the PK of naxitamab 6. Assessment of ADA formation 7. Intravenous (IV) opioid use during cycle 1 defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab 8. Intravenous (IV) opioid use for each cycle during the trial defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab 9. Number of hospitalization days related to naxitamab during cycle 1, defined as number of overnight stays. Hospitalizations required solely for protocol-specified assessments (e.g., PK sampling) or non-medical circumstances are excluded 10. Number and percentage of infusions done in an outpatient setting 11. In patients with positive ADA at trial inclusion, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE, version 4.0 Key secondary endpoints for long term follow-up: 1. PFS, defined as the time from the 1st infusion of naxitamab until PD or death, whichever comes first; data will be censored at the date of last disease evaluation before new anti-NB treatment 2. OS, defined as the time from the 1st infusion of naxitamab until death; data censored at last date known to be alive ;Timepoint(s) of evaluation of this end point: During an | — |
Countries
Canada, Denmark, Germany, Hong Kong, Spain, United Kingdom, United States
Contacts
Public ContactVice President, Clinical
KLIFO A/S
Outcome results
None listed