
    low accrual
  
['glioma', 'diffuse intrinsic pontine glioma']
['panobinostat', 'everolimus']

        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.
      