Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma

* INCLUSION CRITERIA:
* Stage 1 Eligibility (Cohort 1 and 2)

Cohort 1

* Histologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology intra-cranial or spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)- fusion ependymoma of grade I, II or III.
* Has received two or fewer prior chemotherapy regimens

Cohort 2

* Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal RELA-fusion ependymoma of grade I, II or III.
* Has received more than two prior chemotherapy regimens

  * Stage 2 Eligibility (Cohorts 3 and 4)

Cohort 3

* Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III.
* Has received two or fewer prior chemotherapy regimens

Cohort 4

* Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III.
* Has received more than two prior chemotherapy regimens.

  * Patients must have an evidence of tumor progression.
  * Patients must have had prior radiation therapy.
  * Patients must be greater than or equal to 18 years old. Currently, no dosing or adverse event data is available on the use of marizomib in patients \< 18 years of age; therefore, only adults are included in this study. Patients \< 18 years of age will be eligible for future pediatric trials.
  * Patients must have a Karnofsky performance status of greater than or equal to 60.
  * Patients must have adequate organ and marrow function as defined below:
  * leukocytes: greater than or equal to 3,000/microliters
  * absolute neutrophil count: greater than or equal to 1,500/microliters
  * platelets: greater than or equal to 100,000/microliters
  * hemoglobin: greater than or equal to 10 gm/dL (can be achieved by transfusion)
  * Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT): less than or equal to 2.5 X institutional upper limit of normal
  * Bilirubin: \<1.5 mg/dL
  * Creatinine up to 1.5-times upper institutional limits OR estimated glomerular filtration rate (eGFR) within normal as predicted by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (greater than or equal to 60 mL/min/1.73m(2).
  * Negative urine protein or urine protein concentration less than or equal to 60 mg/dL
  * The effects of marizomib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 30 days after the last dose of the drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  * Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* Anticancer treatment within designated period of time before enrollment including:

  * surgery within 14 days
  * needle or core biopsy within 7 days
  * prior cytotoxic therapy within 28 days,
  * vincristine within 14 days
  * nitrosoureas within 42 days,
  * procarbazine administration within 21 days
  * non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid (radiosensitizer does not count) within 7 days; Avastin within 21 days. Any questions related to the definition of non-cytotoxic agents should be directed to the NCI Principal Investigator.
* Treatment with any investigational agent within 28 days before enrollment.
* History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless patient is in complete remission and off all therapy for that disease for a minimum of 3 years.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to marizomib.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Inadequately controlled hypertension (defined as systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90 mmHg).
* Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
* New York Heart Association (NYHA) Grade II heart failure or greater or history of hospitalization for congestive heart failure diagnosis within 12 months prior to enrollment.
* History of myocardial infarction or unstable angina within 3 months prior to enrollment.
* A marked baseline prolongation of QT interval (QT)/corrected QT interval (QTc) (e.g., repeated demonstration of a QTc interval \>480 milliseconds (ms) (CTCAE grade 1) using Frederica's QT correction

formula.

* A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
* Current use of concomitant medications that prolong the QT/QTc interval
* History of stroke or transient ischemic attack within 3 months prior to enrollment.
* Pregnant women are excluded from this study because marizomibs potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with marizomib, breastfeeding should be discontinued if the mother is treated with marizomib.
* Patients receiving combination antiretroviral therapy for treatment of Human Immunodeficiency Virus (HIV) or active anti-viral treatment for Hepatitis A, B or C infection. Anti-viral therapy, when combined with marizomib, poses a potential for pharmacokinetic interactions. Marizomib also increases immunosuppression, placing patients at an increased risk of acquiring lethal infections. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
* Inclusion Criteria for Pregnancy Cohort (P)

Because the drug manufacturer would like to study the effect of the study therapy on pregnancy, and because the required information cannot be collected unless a subject is enrolled per ruling of the OGC, the following additional groups of subjects may be enrolled if necessary.

-A child whose parent (male or female) is/was an active participant in the study at any time during the childs gestation. Active participant is defined as having received at least one dose of study therapy through 6 months after the last dose of study therapy.

OR

* An expectant mother of child whose father is/was an active participant in the study at any time during the childs gestation. The father must have received at least one dose of study therapy. Active participant is defined as having received at least one dose of study therapy through 6 months after the last dose of study therapy.
* The expectant mother must be age 18 or older and must have the capacity to provide informed consent.