Phase II Trial of Naxitamab, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Combination With Induction Chemotherapy for Patients With Newly-Diagnosed High-Risk Neuroblastoma
This clinical trial will evaluate the safety of chemoimmunotherapy with Naxitamab and COG-type induction chemotherapy in newly-diagnosed patients with high-risk neuroblastoma. We aim to recruit 10 patients over the next 2 years.
• Age - 12 months to 21 years at protocol enrollment
• Clinical eligibility criteria:
∙ Newly diagnosed high risk neuroblastoma.
‣ BOTH stage M (INRG - International Neuroblastoma Risk Group) and age ≥547 days.
‣ Patients ≥ 547 days of age who were initially diagnosed with INRG L1 or L2 disease but progress to Stage M without chemotherapy
‣ Patients \< 547 days of age with INRG Stage M or MS disease and patients of any age with INRG L2 with MYCN amplification (v-myc avian myelocytomatosis viral related oncogene)
• Pathology:
∙ Neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis, or
‣ demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
• Molecular testing:
∙ MYCN testing will be done by FISH (Fluorescence In Situ Hybridization) assessment of the FFPE (Formalin-Fixed Paraffin-Embedded) material submitted from the tumor mass. \> 4-fold increase in MYCN signals as compared to reference signals will qualify as MYCN amplified.
‣ ONCOMINE testing will evaluate ALK (Anaplastic Lymphoma Kinase) mutation
• Timing of patient enrollment
∙ Patients will be enrolled up to 6 weeks from primary diagnosis
‣ Pre-study imaging tests are acceptable up to 3 weeks prior to study enrollment and only if done after any pre-protocol chemotherapy.
• Pre-treatment functional status:
∙ No active bacterial infection without adequate antibiotic therapy
‣ No uncontrolled viral infection - decision will be made after infectious disease consultation
‣ No uncontrolled organ dysfunction:
• i. Renal function based on the Schwartz formula (Schwartz et al. J. Peds, 106:522, 1985). If creatinine level is abnormal chemotherapy treatment will be planned in consultation with Nephrology service. Naxitamab will be initiated if creatinine level is up to 1.2 of normal.
• ii. Adequate liver function defined as: -
⁃ Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age,
⁃ and SGPT (Serum Glutamic Pyruvic Transaminase - ALT) ≤ 10 x ULN\* iii. Adequate cardiac function defined as: -
• 1\. Shortening fraction of ≥ 27% by echocardiogram, 2. or Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram.