- - Inclusion Criteria - All Participants:
Age must be ≥ 2 and < 21 years
2. BSA ≥ 0.5 m2
3. Must have measurable or evaluable disease
4. Diagnosis of DIPG (Stratum A), or recurrent/refractory/progressive MBT (WHO Grade
III/IV) or ST, including neuroblastoma, Ewing sarcoma, rhabdomyosarcoma,
malignant rhabdoid tumor and osteosarcoma (Stratum B).
5. Lansky (for participants ≤ 16 years) or Karnofsky (for participants > 16 years)
performance score ≥ 40 at the time of study enrollment
6. Adequate organ function at the time of study enrollment as follows:
7. Bone marrow: ANC ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent
meaning not having had platelet transfusion for 7 days prior to enrollment),
hemoglobin concentration ≥ 8g/dL (may be transfused). Participants with bone
marrow involvement are eligible but not evaluable for hematologic toxicity.
8. Renal: Normal serum creatinine concentration
9. Hepatic: Total bilirubin concentration < 1.5x the institutional upper limit of
normal for age; SGPT < 3x the institutional upper limit of normal
10. Female research participants of childbearing potential (age 10 or greater) must
not be pregnant as confirmed by a serum or urine pregnancy test and confirmed
within 1 week of start of treatment. Participants must not be breast-feeding.
11. Males or females of reproductive potential may not participate unless they have
agreed to use two effective contraceptive methods. Abstinence in a non-sexually
active child will be sufficient birth control.
- - Stratum A - Newly Diagnosed DIPG
Diagnosis of DIPG or high-grade glioma originating from the brainstem
2. Participants have had no previous treatment except corticosteroid use.
3. Participants are able to take abemaciclib as intact capsules by mouth.
- - Stratum B - Recurrent/refractory/progressive MBT (including DIPG) or
Participants must have radiologic evidence of recurrent, refractory or progressive
malignant brain tumor or solid tumor
2. Participants must be able to swallow capsules.
3. Participants with neurological deficits should have deficits that are stable for a
minimum of 1 week prior to registration.
4. Participants who are on dexamethasone must be on a stable or decreasing dose for at
least one week prior to registration.
5. Participants must have fully recovered from the acute toxic effects of chemotherapy,
immunotherapy, or radiotherapy prior to entering this study.
6. Myelosuppressive chemotherapy: Participants must have received their last dose of
known myelosuppressive anticancer chemotherapy at least 21 days prior to study
registration or at least six weeks if nitrosourea. At least two weeks must have lapsed
if participants received lower dose oral etoposide (50 mg/m2) without experiencing
evidence of myelosuppression (i.e. neutropenia or requiring transfusion with blood
7. Biologic agent: Participants must have recovered from any toxicity potentially related
to the agent and received their last dose of the biologic agent ≥ 7 days prior to
8. Monoclonal antibody treatment: At least three half-lives must have elapsed prior to
9. Radiation: Participant has received radiation therapy prior to study registration.
Participants must have had their last fraction of local irradiation to the primary
tumor ≥ 3 months prior to registration, their last fraction of craniospinal
irradiation (>24Gy) or total body irradiation > 3 months prior to registration.
Participant has not received focal irradiation for symptomatic metastatic sites within
14 days prior to registration.
10. Bone Marrow Transplant: Participant must be ≥ 3 months since high dose chemotherapy
and peripheral blood stem cell rescue prior to registration.
11. Growth factors: Participants must be off all colony forming growth factors(s) for at
least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at
least 2 weeks for long-acting formulations (e.g. neupogen).
1. Uncontrolled infection
2. Prior history of QTc prolongation or QTcF > 450 ms on screening ECG.
3. Any concomitant significant medical illness that cannot be adequately controlled with
appropriate therapy, or that would impair the evaluation of side effects related to
this treatment, alter drug metabolism or the tolerance to this treatment
4. Receiving any other anticancer or investigational drug therapy
5. Prior therapy with abemaciclib