NANT 2021-01 Phase II STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial

Eligibility Criteria

• * Patients must be ≥ 1 year and ≤31 years of age at the time of enrollment on the study.
• * Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• * Patients must have high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients whose disease was initially considered low or intermediate risk but then reclassified as high-risk neuroblastoma prior to enrollment also meet this criteria.
• * Patients must have at least ONE of the following:
• * Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below) based on institutional assessment:
• 1. a) MIBG avid tumors: patients must meet one of the following criteria:
• 1. SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for discrete lymph nodes ≥ 15mm on short axis. Lesions meeting size criteria will be considered measurable.
• 2. In addition to size, a lesion needs to meet ONE of the following criteria except for patients with parenchymal CNS lesions which will only need to meet size criteria:
• 1. For MIBG avid tumors: lesion must be MIBG avid and meet one of the following criteria:
• 1. For patients with recurrent/progressive or refractory disease:
• 2. For patients with persistent disease:
• * Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 50 (Appendix I).
• * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration.
• * Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows:
• 1. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration.
• 2. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration.
• 3. Monoclonal antibodies: must not have received last dose within 14 days of registration and resolution of all toxicities.
• 4. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities.
• 5. Radiation: must not have received small port radiation within 7 days prior to registration, large field radiation within 12 weeks, and 131I-MIBG therapy or other radiopharmaceutical within 6 weeks.
• 6. Hematopoietic Stem Cell Transplant- none following myeloblative therapy within 6 weeks
• 7. Any other investigational agents (covered under another IND within 14 days
• 8. Strong inducers or inhibitors of CYP3A4
• * Hematologic Function:
• 1. Absolute Neutrophil count ≥750/µL
• 2. Platelet count ≥ 75,000/µL, transfusion independent (no platelet transfusions within 7 days of blood draw documenting eligibility)
• * Renal Function Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age
• * Liver Function
• 1. Total bilirubin ≤ 1.5 x ULN for age; and,
• 2. SGPT (ALT) ≤ 135 U/L (≤ 3x ULN). Note that for ALT, the upper limit of normal for all sites is defined as 45 U/L.
• * Cardiac Function
• 1. Normal ejection fraction (≥ 55%) documented by either echocardiogram OR
• 2. Normal fractional shortening (≥ 27%) documented by echocardiogram
• * Pulmonary Function No evidence of dyspnea at rest
• * Reproductive Function All females ≥ Tanner stage 2 and post-menarchal of childbearing potential must have a negative beta-HCG within 7 days prior to study registration. Males and females of reproductive age and childbearing potential must commit to using effective contraception for the duration of their participation.
• * Central Nervous System (CNS) Patients with a history of intraparenchymal or leptomeningeal based CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
• * Patients who are pregnant, breast feeding, or unwilling to use effective contraception during the study
• * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• * Patients with disease of any major organ system that would compromise their ability to withstand therapy.
• * Patients with \> Grade 2 diarrhea.
• * Patients who have undergone a prior allogeneic stem cell or solid organ transplant.
• * Patients who are on hemodialysis.
• * Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria.
• * Patients with known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.
• * Patients must not have been diagnosed with any other malignancy.
• * Patients with history of Grade 4 Allergic reactions to anti-GD2 antibody therapy or reactions that caused permanent discontinuation of therapy.
• * Patients with history of progressive disease while receiving therapy per ANBL1221.
• * Patient declines participation in the NANT biology study and the site has not been granted a waiver from participation.
• * Systemic Steroids and Immunosuppressive Medications
• * Patients who have received pharmacologic doses of systemic steroids 7 days prior to study registration or likely to require them after study registration.
• 1. Patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration.
• 2. The use of conventional doses of inhaled steroids for the treatment of asthma
• 3. The use of physiologic doses of steroids for patients with known adrenal insufficiency.
• * Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) at the time of study registration.