Trial of Panobinostat in Children With Diffuse Intrinsic Pontine Glioma

STRATUM 1 - INCLUSION CRITERIA

• DIAGNOSIS - Patients with progressive DIPG or H3K27M+ Thalamic DMG , as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since diagnosis, OR the appearance of a new tumor lesion since diagnosis.
• Please note: patients with a radiographically typical DIPG, 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 malignant glioma WHO II-IV.
• Thalamic Diffuse Midline Glioma patients will be eligible if there is tissue confirmation of the H3K27M mutation by immunohistochemistry or by gene testing performed in a CLIA certified laboratory of the investigator's choice.
• AGE - Patients must be ≥ 2 but 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within 7 days of enrollment must be ≥ 50%. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• PRIOR THERAPY - Patients must have received a minimum of 54 Gy focal irradiation administered over approximately 42 days prior to enrollment. Patients must have recovered from the acute treatment-related toxicities (defined as 3 months prior to enrollment.
• Focal irradiation to the primary site > 42 days prior to enrollment
• Local palliative irradiation other than previously irradiated primary site (small port) ≥ 14 days
• ORGAN FUNCTION - Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,000/mm3
• Platelets ≥ 100, 000/ mm3 (unsupported, defined as no platelet transfusion within 7 days, and recovery from post-transfusion nadir)
• Hemoglobin ≥ 8 g/dl (may receive transfusions)
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN)
• ALT(SGPT) 60 Gy total radiation to the pons (e.g. patients who have received re-irradiation).
• Patients have had prior HDAC, DAC, HSP90 inhibitors for the treatment of their DIPG.
• Patients have had valproic acid within 28 days prior to enrollment.
• Patients have had prior bone marrow transplant.
• NEUROLOGICAL STATUS - Patients have significant acute deterioration in neurologic status in 72 hours prior to enrollment, in the opinion of the treating physician.
• GASTROINTESTINAL
• Patients have impairment of GI function or GI disease that may significantly alter the absorption of panobinostat; for example severe inflammatory bowel disease.
• Patients have diarrhea > CTCAE grade 2.
• SYSTEMIC ILLNESS - Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results.
• OTHER MALIGNANCY - Patients have a history of any other malignancy.
• TRANSFUSIONS - Patients are known to be refractory to red blood cell or platelet transfusions.
• CONCURRENT THERAPY
• Patients who are receiving any other anticancer or investigational drug therapy
• Patients who are required to receive any medication which can prolong the QTc interval. Please see Protocol Appendix B: Medications Which May Cause QTc Prolongation.
• BREASTFEEDING - Female patient IS breastfeeding.
• INABILITY TO PARTICIPATE - Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up