INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas

INCLUSION CRITERIA

Histologic diagnosis:

• Patients with recurrent/progressive high-grade gliomas, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR a ≥ 25% increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since diagnosis utilizing the MRI sequence best demonstrating tumor, OR the appearance of a new/metastatic tumor lesion(s) since diagnosis.
• Eligible diagnoses include but are not limited to the following: diffuse intrinsic pontine glioma (DIPG), H3K27M-altered diffuse midline glioma (DMG), glioblastoma multiforme, anaplastic astrocytoma and anaplastic oligodendroglioma. Spinal cord tumors are eligible with pathologic confirmation of the above.
• Please note: Patients with a radiographically typical DIPG at diagnosis, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation.
• Patients with pontine lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of pontine glioma WHO II-IV.
• Patients with diffuse or multi-focal disease are eligible; patients with leptomeningeal spread are eligible.

Age

• Patients must be ≥ 3 but ≤ 21 years of age at the time of enrollment.

BSA

• Patients must have a BSA ≥ 0.70-2.50 m2 for dose 120 mg/m2/dose BID.
• Patients must have a BSA ≥ 0.55-2.80 m2 for dose 80 mg/m2/dose BID (Patients who have BSA 0.55-1.00 m2 will only receive 100 mg AM dose).

Ability to Swallow

• Patients must be able to swallow tablets whole.

Measurable disease

• Patients must have measurable disease in two dimensions on MRI to be eligible.

Prior Therapy

• Patients must have failed at least 1 standard, tumor-directed treatment besides surgery and recovered from the acute treatment-related toxicities (defined as 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50.

Organ Function: Patients must have adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥ 1.0 x 10^9 cells/ L
• Platelets > 100 x 10^9 cells/ L (unsupported, defined as no platelet transfusion within 7 days)
• Hemoglobin ≥ 8 g/dL (may receive transfusions)
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN)
• ALT (SGPT) and AST (SGOT) 95th percentile for age, height, and gender; patients with values above these levels must have their blood pressure controlled with medication prior to starting study drug).
• The normal blood pressure by height, age, and gender tables can be accessed in the Generic Forms section of the PBTC member's webpage.
• Patients who are ≥ 18 years of age must have blood pressure that is < 140/90 mm of Hg at the time of registration.

Concomitant Medications

• Patients who are receiving any other anti-cancer, investigational or alternative (e.g., cannabinoids) drug therapy are ineligible.

Prisoners

• Prisoners will be excluded from this study.

Inability to participate

• Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures and study restrictions.

Allergy

• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition.
• Patients with a history of allergy to pork products due to contraindications with low molecular weight heparin (LMWH).

Thrombosis Risk

• Patients with a known coagulopathy or bleeding disorder (e.g., von Willebrands disease) are not eligible.
• Patients with a history of non-central line related thrombosis or disorders that promote clotting (e.g., anti-thrombin III d