A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients with Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

Y-mAbs Therapeutics A/S0 个研究点目标入组 122 人开始时间: 2017年12月4日最近更新: 2024年2月26日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 122

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•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 patients with either primary 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 at screening, (hematological support is allowed if administered =1 week before first screening procedure), defined as:
•a. Hemoglobin =8 g/dL (5.0 mmol/L)
•b. White blood cell count =1000/µL (1.0e9/L)
•c. Absolute neutrophil count (ANC) =500/µL (0.5e9/L)
•d. Platelet count =25,000/µL (25e9/L)
•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: 116
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 6
•F.1.3 Elderly (>=65 years) no
•F.1.3.1 Number of subjects for this age range

排除标准

•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 according to Park criteria (Park et al. 2017) (see section 6.7)
•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 42 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
•17. Treatment with immunosuppressive agents (local steroids excluded) within a month prior to 1st dose of GM-CSF.
•18. Inadequate cardiac function defined as either left ventricular ejection fraction of < 50% by echocardiography or other clinically relevant cardiac disorders at the discretion of the investigator.

研究者

发起方

Y-mAbs Therapeutics A/S

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