Clinical Trial Finder

Inclusion Criteria:

• - All patients and/or a legal guardian must sign institutionally approved written informed consent and assent documents.

• - Patient must be greater than 2 years and less than 30 years.

• - BSA (body surface area) greater than 0.3 m2.

• - Functional status: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients < 16 years of age (Karnofsky and Lansky is a scoring system used to quantify the general well being of cancer patients where 100% represents perfect health and 0% represents death).

Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 7 days. Patients who are unable to walk because of paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

• - Adequate bone marrow function.

• - Adequate liver function.

• - Adequate renal and metabolic function.

• - Urine protein:creatinine (UPC) ratio of < 1; or a urinalysis that is negative for protein; or 24-hour urine protein level < 1000 mg/dL.

• - Patients must have Magnesium > 1.5 mg/dL and potassium > 3.5 mmol/L.

• - Patients with known seizure disorder must have seizures adequately controlled with non- enzyme inducing antiepileptic medications.

• - No increase in steroid dose within the past 7 days.

• - STRATUM A: histological confirmation of a newly diagnosed high-grade glioma or DIPG or STRATUM B: histological confirmation of a recurrent or progressive grade II-IV glioma (including DIPG) [histology can come from tissue at diagnosis or relapse] - Primary brain or spine tumor are eligible, including tumors with metastases, multiple lesions.

• - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.

• - Myelosuppressive chemotherapy: Must not have received within 3 weeks (6 weeks if prior nitrosourea).

• - Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor, 14 days for long-acting (e.g. PEG-filgrastim) - Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is longer) since the completion of therapy with a biologic agent.

• - Radiation therapy: Strata A: ≥ 2 weeks and ≤ to 12 weeks must have elapsed from radiation.

Strata B: ≥ 2 weeks must have elapsed from focal radiation.

• - Surgery: > 3 weeks from major surgery.

If recent craniotomy, adequate wound healing must be determined by neurosurgical team.

• - Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 4 weeks must have elapsed.

• - H3K27M mutation: Participants must have a mutation in H3.3 K27M or H3.1 K27M as identified by tumor (FFPE or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing, or by CLIA-certified immunohistochemistry staining positive for H3K27M, as defined by review by U of M neuro-pathology.

Exclusion Criteria:

• - Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded.

Abstinence is considered an effective form of birth control.

• - Patients with uncontrolled infection are excluded.

• - Inability to swallow oral pill (panobinostat does not have liquid formulation).

• - Other medications: Patients receiving other anti-neoplastic agents are excluded; patients on enzyme-inducing anticonvulsive agents are excluded; patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded; patients on steroids for symptom management must be on a stable dose for 7 days prior to start of treatment.

• - Allogeneic stem cell transplant: Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD or requiring immunosuppression are excluded.

• - Previous hypersensitivity to rapamycin or rapamycin derivatives.

• - Baseline QTc of >450 msec on EKG OR electrolyte imbalance predisposing to QTc prolongation (baseline ≥ Grade 1 hypokalemia or hyperkalemia; and baseline ≥ Grade 2 Ca++, Mg++, phosphate abnormalities).

Repletion/correction is allowed to achieve eligibility. Use of QTC prolonging medications will be monitored throughout the trial.

Arms

Experimental: Panobinostat and Everolimus

Panobinostat daily M, W, F for 2 weeks every 28 days for the first cycle (28 days). After first cycle Panobinostat daily M, W, F for 2 weeks every 28 days combined with Everolimus daily.

Interventions

Drug: - Panobinostat

30 mg/m^2

Drug: - Everolimus

3.0 mg/m^2