A Phase I/II Study of Ribociclib,a CDK4/6 Inhibitor, Following Radiation Therapy

Inclusion Criteria: * Age * Patients must be ≥ 12 months of age and ≤ 30 years of age at the time of study entry for patients diagnosed with DIPG. * Patients must be ≥ 12 months of age and ≤ 21 years of age at the time of study entry for patients diagnosed with HGG. * RB status * Diagnostic stereotactic biopsy: Patients diagnosed with DIPG may choose to have a stereotactic biopsy prior to starting radiation therapy. * Toxicities related to biopsy must have resolved prior to proceeding with radiation therapy. * Screening for Rb applies to all patients with available tissue except for patients diagnosed with DIPG and bi-thalamic tumors. * If resection occurred at an outside institution, eligibility and treatment MRI evaluations in addition to Rb testing must be completed at CCHMC. * Tumor * Diffuse Intrinsic Pontine Glioma (DIPG) Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined on neuroimaging as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation. * Patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to have + RB and be the following according to the 2016 World Health Organization classification of tumors of the central nervous system: an anaplastic astrocytoma (IDH mutant, IDH wildtype, or NOS), glioblastoma (IDH mutant, IDH wildtype or NOS), diffuse midline glioma, H3 K27M mutant or H3 K27M negative, diffuse astrocytoma (IDH mutant, IDH wildtype or NOS). * Note: Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, pleomorphic xanthoastrocytoma with or without anaplasia, gangliogliomas, or other mixed gliomas without anaplasia are not eligible. * Patients with diffuse intrinsic brain stem glioma (DIPG) can be enrolled without the need for available tumor tissue for RB protein status confirmation. * Bi-thalamic tumors, biopsied and noted to have intact RB. Bi-thalamic tumors that are not biopsied will be eligible to enroll on the DIPG/bi-thalamic non-biopsied arm. * High-grade Glioma (HGG) * Patients must have had histologically verified the following according to the 2016 World Health Organization classification of tumors of the central nervous system: anaplastic astrocytoma (IDH mutant, IDH wildtype, or NOS), glioblastoma multiforme (IDH mutant, IDH wildtype, or NOS), diffuse astrocytoma (IDH mutant, IDH wildtype or NOS) * AND RB positive noted on immunohistochemistry. * Patients with primary spinal cord tumors are eligible. Patients with multi-focal disease within the cerebrum are eligible. * Patients with a diagnosis of oligodendroglioma or oligoastrocytoma are not eligible. * Performance Status • Karnofsky \> 50 % for patients \>16 years of age or Lansky \> 50 for patients \< 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Prior Therapy • Patients must have not received any prior therapy other than surgery, radiation and/or steroids. * Radiation therapy requirements * Patients diagnosed with DIPG: any variances in the radiotherapy dose within 10% of the current standard dose (54 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment * Patients diagnosed with HGG: any variances in the radiotherapy dose within 10% of the current standard dose (59.4 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment. * Patients diagnosed with primary spinal tumors any variances in the radiotherapy dose within 10% of the current standard dose (54 Gy) will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment. * Timing of Radiation - radiation therapy must begin no later than 30 days after the date of radiographic diagnosis or definitive surgery, whichever is the later date. * Organ Function * Patients must have normal organ and marrow function documented within 7 days of study enrollment as defined below: * Absolute neutrophil count ≥ 1000mm3 * Platelets ≥ 75,000/mm3 (unsupported for 7 days) * Hemoglobin ≥ 9g/dl (unsupported) for 7 days * Total bilirubin ≤ 3 times upper limit of normal (ULN) for age * ALT (SGPT) ≤ 2.5 X ULN for age * Albumin ≥ 2 g/dl * Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73m2 or serum creatinine based on age/gender. * Pregnancy Status Female patients of childbearing potential, must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test. * Pregnancy Prevention Patients of childbearing or child fathering potential must use a highly effective method of contraception throughout the study while taking the drug and for 21 days after stopping treatment * Female patients with infants must agree not to breastfeed their infants while on this study. * Informed Consent Signed informed consent according to institutional guidelines must be obtained. Assent, when appropriate, will be obtained according to institutional guidelines. Exclusion Criteria: * Concurrent Illness Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results. * Inability to Participate Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. * Received a radiosensitizer or any additional adjuvant therapy during radiation therapy. * Patients with disseminated disease to the spine are not eligible, and MRI of spine must be performed prior to enrollment if the treating physician suspects disseminated disease. * Seizures Patients who are currently receiving enzyme inducing anti-epileptic drugs that are known strong inducers or inhibitors of CYP3A4/5 (EIAEDs). Patients with a history of seizures and maintained on an anti-epileptic drug that is not a strong inducers or inhibitor of CYP3A4/5 are eligible. * Patient has a known hypersensitivity to Ribociclib or any of its excipients. * Clinically significant active cardiac disease, uncontrolled heart disease and/or history of cardiac dysfunction including any of the following * History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy * Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50 % as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening * History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening * Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. * Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication * Hypertension defined below: * Patients 2-17 years of age must have a blood pressure that is ≤ 95th percentile for age, height and gender at the time of enrollment. * Patients who are ≥ 18 years of age must have a systolic blood pressure that is \> 160 or diastolic \< 90 mm of Hg at the time of enrollment * Note: If a BP reading prior to enrollment is above the 95th percentile for age, height and gender, it is to be rechecked and documented to be ≤ 95th percentile for age, height and gender prior to patient enrollment. * Inability to determine the QTcF interval on the ECG (i.e. unreadable or not interpretable) or QTcF \> 450 msec (using Fridericia's correction). All as determined by screening ECG (using the mean QTcF of triplicate ECGs) * Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug Ribociclib: * Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges * Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 * Medications that have a known risk to prolong the QT interval or induce Torsades de Pointes * Herbal preparations/medications, dietary supplements. * Patient is currently receiving warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed * Patient has a history of non-compliance to medical regimen. * Known need for major surgery within 14 days of the first dose of Ribociclib. Gastrostomy, insertion of a G tube, Ventriculo-peritoneal shunt, endoscopic ventriculostomy and central venous access are NOT considered major surgery.