Trial of NLG802 Indoximod Prodrug Plus Temozolomide for Patients With Progressive Pediatric Brain Cancer

Prior treatment

• Active therapy for radiation necrosis.

Other illness

• Clinically significant cardiovascular disease.
• Active systemic infection requiring treatment.
• Active autoimmune disease that requires systemic therapy.
• Any known bleeding diathesis.

Lab values

• Baseline QTcB of \> 470 msec at screening, and subjects with known congenital long QT syndrome.

Other

• Unable to swallow capsules.
• Subjects who are breastfeeding or pregnant women.

• Age must be ≥ 5 years and \< 22 years.
• Subjects must have relapsed or treatment-refractory primary brain or spinal malignancy of any histology.
• Subjects are allowed to have surgical debulking and/or radiation/proton therapy prior to enrollment in this trial.
• Tumor tissue is required for central review of tissue diagnosis and biomarker correlate studies.
• Collection of baseline blood samples for required biomarker correlate trials.
• Performance score: Lansky or Karnofsky performance status score must be ≥ 70.
• Life expectancy must be ≥ 3 months.
• Hemoglobin ≥ 10 g/dL
• Platelets ≥ 100,000/μL
• ANC ≥ 1,000/μL
• ALT ≤ 3-times upper limit of normal.
• Total bilirubin ≤ 1.5-times upper limit of normal.
• Adequate renal function
• Seizure disorders must be well controlled with antiepileptic medication.
• Subjects must be able to swallow pills.
• Corticosteroid therapy: When necessary for adrenal replacement, subjects may receive hydrocortisone ≤ 1.7 mg/kg/day, maximum dose 70 mg/day (or equivalent).
• At the time of starting protocol therapy, subjects must be ≥ 21 days from the administration of any prior cytotoxic therapy (including chemotherapy).
• At the time of starting protocol therapy, subjects must be ≥ 28 days from any radiation or proton therapy.
• At the time of starting protocol therapy, subjects must be ≥ 28 days from administration of antibody-based immune checkpoint-inhibitor therapies, tumor-directed vaccines, or cellular immune therapies.
• At the time of starting protocol therapy, subjects must be ≥ 56 days from administration of tumor-directed therapies using infectious agents.
• At the time of starting protocol therapy, subjects must be ≥ 90 days from a stem cell transplant with growth-factor independent recovery of adequate bone marrow function.
• Subjects, or their parent for subjects \< 18 years of age, must sign an Informed Consent Form (ICF) indicating that they understand the purpose of the trial and procedures required, including biomarkers, and are willing to participate in the trial.