Testing hu1418K322A + Temozolomide + Irinotecan for high-risk neuroblastoma

Inclusion

• +Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study except to manage allergic reactions
• +Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy.
• +Are initially diagnosed with histologically proven HRNB with metastatic disease.
• +Any active uncontrolled infection at the time of enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →. Any known history of infection with human immunodeficiency virus (HIV), or active or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• +Are ≥18 months to \<18 years of age at time of informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → or assent.
• +Have evaluable or measurable disease per International Neuroblastoma Response Criteria (INRC)
• +Have a Lansky performance status of ≥50 (≤16 years ) or Karnofsky performance status ≥50% (for \>16 years).
• +Have recovered from the toxic effects of prior chemotherapies
• +Meet the following organ function criteria, as measured within 1 week prior to Investigational Medicinal Product (IMP) dosing:
• +BM function: i. Platelets ≥50 × 109/L ii. Absolute neutrophil count (ANC) ≥0.50 × 109/L
• +Renal function: i. Age-adjusted serum creatinine ≤1.5 × upper limit of normal (ULN) for age. ii. Estimated glomerular filtration rate (eGFR) at least 60 mL/min using the Schwartz formula.
• +Liver function: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN and total bilirubin ≤1.5 × ULN.
• +Cardiac function: i. Shortening fraction ≥27% or ejection fraction of ≥50% on echocardiogram. ii. Corrected QT Interval on electrocardiogram (ECG) using the Fridericia formula (QTcF) ≤ 480 msec.
• +Lung function: i. Pulse oximetry considered normal in room air. No evidence of dyspnea at rest.
• +Central nervous system (CNS) function: i. Participants with a history of CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
• +If applicable based on age, are willing and able to provide voluntary written informed assent for participation in the study (as per local Institutional Review BoardResearch Ethics Board (REB)The independent committee that must approve a study before it can run.Read more → \[IRB\]/Independent Ethics Committee \[IEC\] requirements and if applicable based on regional age of consent) and to comply with all protocolProtocolThe detailed plan a study must follow.Read more → requirements.
• +Their parent or legal guardian (if applicable based on regional age of consent) is willing and able to provide voluntary written informed consent for the participant's involvement in the study.
• +Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +Any contraindications to any of the study treatments.
• +Patients with \>Grade 2 diarrhea.
• +Patients who have undergone a prior allogeneic stem cell transplant \< 6 months ago or have undergone a solid organ transplant.
• +Patients who are on hemodialysis.
• +Patients on any other immunosuppressive medications
• +Patients who have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment.
• +Patients who have been diagnosed with any malignancy other than neuroblastoma.
• +Patients with symptoms of congestive heart failure.
• +Patients participating in or planning to participate in another study that is either blinded or involves an IMP
• +Do not meet the following required washoutWashout periodA gap with no treatment, so the previous one clears your system.Read more → periods prior to the administration of the first dose of hu14.18K322A:
• +7 days from prior systemic biologic antineoplastic agents (e.g. anti-cancer agents not known to be myelosuppressive - not associated with reduced platelet or ANC counts).
• +14 days from systemic steroids.
• +6 weeks from prior craniospinal radiotherapy or Iodine-131-metaiodobenzylguanidine (131I-MIBG) therapy.
• +2 weeks from radiotherapy to the primary tumor bed.
• +14 days or 5 half-lives (whichever is longer) from last administration of an IMP.
• +\>7 days prior to study enrollment for drugs that are strong inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4).
• +≥21 days and with recovery of all associated toxicities from receiving cellular therapy (e.g., modified T lymphocyte cells, Natural Killer (NK) cells, dendritic cells).
• +Ongoing need for any medication known or suspected to interfere with study treatment.
• +If a fertile and sexually active woman of child-bearing potential (WOCBP), have a negative serum pregnancy test at ScreeningScreeningThe checks done before joining, to see whether a study fits.Read more → and then either a negative serum or urine test prior to each cycle and agree to use an acceptable and highly effective contraception method during the study and for at least 6 months after the last day of study treatment .
• +If a fertile and sexually active male, agree to use condoms during the study and for at least 6 months after the last dose of study treatment
• +If female, are breastfeeding, pregnant, or planning to become pregnant, or, if sexually active and of child-bearing potential, are unwilling to use an effective birth controlControl groupThe group a new treatment is measured against.Read more → method until 6 months after the last dose of study medication
• +Are at least 2 weeks beyond any major tumor surgery
• +Patients with disease of any major organ system that would compromise their ability to withstand chemoimmunotherapy.
• +14 days from prior systemic myelosuppressive chemotherapy.
• +≥12 weeks from large field radiation therapy (i.e., total body irradiation, whole abdominal, total lung, ≥50% pelvis).
• +≥7 days from small treatment field radiation.