Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Gliosarcoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Proteasome Inhibitors

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Part1-Phase1: MRZ 10 minute IV infusion on Days 1, 8, and 15 plus BEV IV infusion on Days 1 and 15 of each 28-day cycle.

Part2-Phase2: MRZ 10 minute IV infusion administered on Days 1, 8, and 15 of each 28-day cycle.

Part3-Phase2: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion on Days 1, 8, and 15 of every 28-day cycle using intra-patient dose escalation. Starting dose will be 0.8 mg/m2.

Part4- Phase1: All subjects will receive MRZ enterally by NG tube as a bolus on Days 1, 8 and 15 of the first 28-day cycle and BEV IV infusion on Day 15 of the first 28-day cycle. For subsequent 28-day treatment cycles, MRZ will be administered as an IV at the recommended dose and schedule determined in Part 1, with BEV IV on Days 1 and 15.

Part5-Phase1: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion at 0.8 mg/m2 on Days 1, 8, and 15 of every 28-day cycle 0.8 mg/m2

MRZ dosing in Phase 1 to range from 0.55 to 0.8 mg/m2. Dose Escalation: MRZ dose-escalation will occur using a standard 3+3 study design.

The RP2D of MRZ (0.8.mg/m2) will be used in a two stage design, with fifteen response-evaluable patients entered in the first stage. If 1 or more responses are observed at the MRZ RP2D, then the second stage will be implemented with an additional 15 response-evaluable patients treated.

BEV 10 mg/kg IV infusion administered for all cohorts in Phase 1 only.

Ileana Elias, MD

This is a Phase 1/2 clinical trial to evaluate a new combination of drugs, marizomib (MRZ) and bevacizumab (BEV; Avastin®), for the treatment of WHO Grade IV malignant glioma. The study population includes subjects who are in first or second relapse and who have not previously received any bevacizumab or other anti-angiogenic agent or proteasome inhibitor for treatment of malignant glioma. Part 1 Phase 1 evaluates the combination of MRZ and BEV, while Part 2 Phase 2 evaluates single-agent MRZ. Part 3 (Phase 2) includes a combination MRZ using intra-patient dose escalation, and BEV at a fixed dose. Part 4 Phase 1 evaluates MRZ through enteral administration, and BEV at a fixed dose. Part 5 Phase 1 evaluates the repeat-dose pharmacokinetics of MRZ administered IV with ECG.

One of the few treatment options currently FDA approved for recurrent WHO Grade IV malignant glioma is BEV. Additional treatment options are needed for these subjects. Published literature indicates that targeting the proteasome in glioma cells has shown significant anti-tumor activity.

MRZ is a novel, second generation proteasome inhibitor that prevents the breakdown of proteins involved in signal transduction which blocks growth and survival of cancer cells. In-vitro studies of multiple glioma cell lines were highly sensitive to MRZ. MRZ had relatively little effect on neural stem/progenitor cells suggesting minimal neurotoxicity while significantly affecting both malignant glioma stem cells and glioma cell lines.

Parts 1 and 2 of this trial have been completed with the Recommended Part 3 (Phase 2) Dose established at 0.8 mg/m2. Part 3 of this trial is enrolling at the MRZ RP2D determined in Phase 1 to assess the combination of MRZ and BEV activity and safety.

Parts 1, 2, 3 and 4 of this trial have been completed with the Recommended Dose established at 0.8 mg/m2. Part 5 of this trial is enrolling.

Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab

Phase 1, Multicenter, Open-label, Dose-escalation, Combination Study of Marizomib and Bevacizumab in Bevacizumab-Naïve Subjects With WHO Grade IV Malignant Glioma Followed by Phase 2 Studies of Single Agent Marizomib and Combination Marizomib and Bevacizumab, and Phase 1 Dose-Escalation Study of Enterally-administered Marizomib With Bevacizumab

Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by the investigator, according to RANO 2010 criteria.

Tumor response assessment was conducted every 2 cycles of study therapy. 95% confidence interval from exact binomial distribution (Clopper-Pearson method).

OS is defined as time from the date of the first dose of study drug to date of death due to any cause. Participants who are alive will be censored at the last follow up visit

Number of subjects experiencing at least 1 Treatment-Emergent Adverse Event (TEAE) within the timeframe specified.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV)

Number of subjects experiencing at least 1 Serious Adverse Event (SAE) within the timeframe specified.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV)

Number of subjects experiencing at least 1 DLT event within the timeframe specified.

DLT is defined as the occurrence of any of the following AEs related to one of the drugs or the combination observed during Cycle 1, using NCI-CTCAE (v 4.03):

* ≥ Grade 3 thrombocytopenia or Grade 2 thrombocytopenia with bleeding.
* Grade 4 neutropenia or anemia lasting for more than 4 days.
* Febrile neutropenia.
* Any ≥ Grade 2 neurological event lasting more than 4 days.
* Grade 3 or 4 non-hematologic toxicity (excluding alopecia), lasting for more than 4 days despite adequate supportive therapy or preventing the next scheduled dose from being administered within 4 days of scheduled day; for ≥ Grade 3 fatigue to be considered a DLT, it must be present for more than 7 days.

For Part 4, data are presented separately for Cycle 1 (when Marizomib was enterally-administered) and for Cycles 2 and subsequent cycles (when Marizomib was administered IV).

DLT was assessed only for Part 1 and Part 4 cohorts.

Number of subjects experiencing at least 1 DLAE within the timeframe specified.

DLAEs are defined as Marizomib-related AEs observed which are:

* related to disturbances in the cerebellum (ie, ataxia, dizziness, dysarthria, fall, gait disturbances) plus hallucinations of any grade
* any other AEs of Grade ≥ 2. DLAEs were assessed only for Part 3 cohorts.

Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by the investigator, according to RANO 2010 criteria.

Tumor response assessment was conducted every 2 cycles of study therapy. 95% confidence interval from exact binomial distribution (Clopper-Pearson method).

Radiographic ORR was assessed for Part 1 and Part 3 cohorts

PFS is defined as the time between start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurs first. Disease progression will be determined using RANO 2010 criteria as assessed by the investigator.

PFS was determined using Kaplan-Meier product-limit estimates.

Triphase

Celgene

Marizomib 0.55 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 1 Cohort 1

Marizomib 0.7 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 1 Cohort 2

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle.

MTD = Maximum Tolerated Dose

Part 1 MTD + Dose Expansion Cohort

Marizomib 0.8 mg/m2 on Days 1, 8, and 15 of each 28-day cycle

Part 2 Cohort

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. Based on presence of dose-limiting adverse events, participants did not escalate Marizomib to a dose of 1.0 mg/m2

Part 3 Cohort 1

Marizomib 0.8 mg/m2 on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. Based on lack of dose-limiting adverse events for at least 1 cycle, participants were allowed to escalate Marizomib to a dose of 1.0 mg/m2

Part 3 Cohort 2

Marizomib 0.075 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 1

Marizomib 0.225 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 2

Marizomib 0.675 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 3

Marizomib 1.0 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 4

Marizomib 1.35 mg/m2 enterally-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle. From Cycle 2, Marizomib was administered at a dose of 0.8 mg/m2 IV

Part 4 Cohort 5

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

All treated participants in Part 2 Cohort

Radiographic Objective Response Rate (ORR) - Part 2 Cohort

Overall Survival (OS) - Part 3 Cohorts

Marizomib 0.075 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 1 - Cycle 1

Marizomib 0.225 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 2 - Cycle 1

Marizomib 0.675 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 3 - Cycle 1

Marizomib 1.0 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 4 - Cycle 1

Marizomib 1.35 mg/m2 enterally-administered on Days 1,8, and 15 + Bevacizumab 10 mg/Kg on Days 1 and 15

Part 4 Cohort 5 - Cycle 1

Marizomib at different dosage IV-administered on Days 1,8, and 15 of each 28-day cycle + Bevacizumab 10 mg/Kg on Days 1 and 15 of each 28-day cycle

Part 4 All Cohorts - Cycles 2 and Subsequent

Number of Participants Experiencing Adverse Events

Number of Participants Experiencing Serious Adverse Events (SAEs)

All treated participants in Part 1 and Part 4

Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

Number of Participants Experiencing Dose-Limiting Adverse Events (DLAEs)

All treated participants with available measurements

Radiographic Objective Response Rate (ORR)

Progression Free Survival (PFS)

Overall Survival (OS)

Overall Study

Symptoms and General Pathology

Recurrence

Diffuse Intrinsic Pontine Glioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Tumor, Childhood

Childhood Brain Stem Glioma

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

All patients will initially receive marizomib (MRZ) alone (Course A1) The dose escalation and de-escalation for single agent and combination will be guided using the Bayesian optimal interval (BOIN) design

-Intravenously initially given every other week over a 28 day course but may go to weekly x 3 and weekly x 4 as the dose levels increase. Up to 26 courses.

If tolerated,combination of Marizomib: and panobinostat on subsequent cycles. The dose escalation and de-escalation for single agent and combination will be guided using the Bayesian optimal interval (BOIN) design.

* Intravenously initially given every other week over a 28 day course but may go to weekly x 3 and weekly x 4 as the dose levels increase. Up to 26 courses.
* Panobinostat: Oral dosage is given 3 times weekly, every other week over a 28 day course

- Intravenously initially given every other week over a 28 day course but will go to weekly x 3 and weekly x 4 as the dose levels increase Up to 26 courses.

Marizomib

- Panobinostat: Oral dosage is given 3 times weekly, every other week over a 28 day course

Katherine Warren, MD

This research study is evaluating the safety, tolerability and preliminary efficacy of the drugs marizomib and panobinostat in pediatric patients with diffuse intrinsic pontine glioma (DIPG).

The names of the study drugs involved in this study are:

* Marizomib
* Panobinostat

This research study involves chemotherapy as a possible treatment for pediatric patients with Diffuse intrinsic pontine glioma (DIPG)

* The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
* The names of the study drugs involved in this study are:

  * Marizomib
  * Panobinostat

This study consists of 2 parts:

* Part A : The investigators are looking at the highest dose (up to a targeted maximum dose) of the study drug Marizomib that can be administered safely without severe or unmanageable side effects in participants that have DIPG, not everyone who participates in this research study will receive the same dose of the study intervention. The dose given will depend on the number of participants who have been enrolled prior and how well the dose was tolerated.
* Part B: Participants who tolerate Marizomib alone will be treated with Marizomib and panobinostat, but at lower dose of marizomib than the dose of marizomib when given alone.

Participants are expected to be on study treatment for up to 2 years followed for up to 5 years.

It is expected that up to 45 people will take part in this research study. This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

* Marizomib has not been approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease.

  -- This is the first time Marizomib will be given to children.
* Panobinostat has not approved by the U.S. Food and Drug Administration (FDA) for the treatment of diffuse intrinsic pontine glioma but it has been approved for other uses.

Phase I Study of Marizomib + Panobinostat for Children With DIPG

Phase 1 Trial of Marizomib Alone and in Combination With Panobinostat for Children With Diffuse Intrinsic Pontine Glioma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

To determine the toxicity profile and any dose-limiting toxicity (DLT) of marizomib as a single agent at doses up to 0.8 mg/m2 , in children with DIPG

To determine the toxicity profile and any DLT of marizomib at doses up to 0.8 mg/m2 when administered in combination with panobinostat to children with DIPG

To estimate the maximum-tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of marizomib when administered as a single agent in children with DIPG

To estimate the MTD or RP2D of marizomib when administered in combination with panobinostat in children with DIPG

Estimated using compartmental methods. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form

Estimated using compartmental methods Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form

Kaplan-Meier method will be used to summarize the time-to-event endpoints, i.e. OS

determined by combination of radiographic assessment, symptoms (patient/parent-reported), clinical (physician or NP) assessment, steroid use, ability to walk, and quality of life (QOL) measure

Secura Bio, Inc.

Dana-Farber Cancer Institute

Principal Investigator

This is an expanded access program (EAP) for eligible participants designed to provide access to Marizomib.

Expanded Access for Marizomib

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Pomalidomide

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Combination Pomalidomide, low-dose Dexamethasone, and Marizomib:

Oral Pomalidomide, days 1-21 of 28 day cycle, dose 3 to 4 mg

pomalidomide

IV Marizomib, 0.2 to 0.5 mg/m2 on days 1, 4, 8, 11 of 28 day cycle

marizomib

Oral Dexamethasone, days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of 28 day cycle, 5 or 10 mg

low-dose dexamethasone

Steven D Reich, MD

This is a Phase 1 clinical trial to evaluate a new combination of drugs for the treatment of relapsed or refractory (drug-resistant) multiple myeloma. The drugs being studied are:

* Pomalidomide (POMALYST®) is a drug that affects the immune system (an immunomodulatory drug) that has been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of multiple myeloma.
* Marizomib is an investigational drug being developed by Triphase that is being studied for the treatment of multiple myeloma. Investigational drugs are drugs that have not yet been approved by health authorities, such as the FDA, for general use but have been approved for use in specific clinical studies. Marizomib inhibits a cellular machine called the proteasome, which destroys unnecessary or damaged proteins. Other proteasome inhibitors have been shown to be effective in the treatment of multiple myeloma.
* Dexamethasone is a corticosteroid drug that affects the immune system (an immunomodulatory drug) that has been approved by the FDA for the treatment of multiple myeloma.

This is the first study to evaluate the three-drug combination of pomalidomide (POM), marizomib (MRZ), and dexamethasone (LD-DEX) in humans. Pomalidomide, alone or in combination with dexamethasone, is approved by the FDA for the treatment of relapsed or refractory multiple myeloma.

The primary objective of this study is to determine the best drug dosing levels for this three-drug combination, including the highest safe doses and/or the recommended doses for future clinical studies of this drug combination. The secondary purposes of this study are to determine the safety of this drug combination and its effectiveness in treating relapsed or refractory multiple myeloma. The study will include examination of levels of all three drugs in the blood during various time points during treatment.

Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma

A Phase 1, Multicenter, Open-label, Dose-Escalation Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

Celgene Corporation

Disease Progression

Ependymoma

Anaplastic Ependymoma

Marizomib at days 1, 8, and 15 of each 28-day cycle

Data collection on pregnancy, birth and Health of Child

0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total.

Mark R Gilbert, M.D.

Background:

Ependymomas are rare tumors that arise from the ependyma. That is a tissue of the central nervous system. They can develop in the brain or the spine. They are usually treated with surgery, radiation, and/or chemotherapy. Researchers want to see if the new drug marizomib can help people with a certain kind of ependymoma.

Objective:

To see if marizomib stops tumor growth and prolongs the time that the tumor is controlled.

Eligibility:

Adults age 18 and older who have been diagnosed with ependymomas and have already been treated with standard therapies

Design:

Participants will be screened with the following tests or recent results from similar tests:

* Medical history
* Physical exam
* Neurological assessment
* Electrocardiogram (EKG) to evaluate the heart
* Review of symptoms and ability to perform normal activities
* Computed tomographic scan (CT) or magnetic resonance imaging (MRI) to produce an image of the brain or spine.
* Blood and urine tests
* Tests of tumor samples. Participants may have to have new tumor samples taken.

Participants will get the study drug in cycles. Each cycle is 4 weeks. Participants will have up to 24 cycles.

Participants will get the study drug through a small plastic tube in a vein on days 1, 8, and 15 of each cycle.

During each cycle, some screening tests will be repeated.

Participants will answer questions about their general well-being and functioning.

About 4 5 weeks after finishing the study drug, participants will have a follow-up visit. They will answer questions about their health, get a physical and a neurological exam, and have blood tests. They may have an MRI or CT scan.

...

Background:

* Ependymomas are rare primary brain tumors arising from radial glial stem cells. They comprise 5.2% of all pediatric primary brain tumors and 1.9% of all adult primary brain tumors.
* The standard therapy for newly diagnosed ependymoma is gross total resection followed by radiation therapy. For anaplastic ependymoma, recurrence rate is high with a median progression free survival (PFS) of 2.3 years.
* There are limited chemotherapy options for recurrent ependymomas, which have already been irradiated. Therefore, there is an unmet need to target novel pathways for treatment of ependymomas.
* About 70% of supratentorial ependymomas have a characteristic signature C11 orf95-V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA) fusion which drives tumorigenesis in ependymomas by activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) transcription pathway.
* Marizomib is a second-generation irreversible proteasome inhibitor which penetrates across the blood-brain-barrier (BBB). It inhibits the activity of 20S proteasome in glioma cells, activates caspases, builds up reactive oxygen species and thus induces apoptosis. Marizomib blocks the NF-pathway by proteasome inhibition. Thus, it may have an additional targeted therapeutic effect in the RELA-fusion molecular subgroup of ependymomas.

Objective:

-To evaluate the efficacy of treatment with marizomib in RELA-fusion recurrent ependymoma and non RELA-fusion recurrent ependymoma as measured by progression-free survival at 6 months (PFS6).

Eligibility:

* Histologically proven intra-cranial or spinal ependymoma.
* Radiographic evidence of tumor progression
* Patients must be greater than or equal to 18 years old.

Patients must have had prior radiotherapy.

Design:

* This is a phase II study to determine the efficacy of marizomib in recurrent ependymoma.
* A novel 2-stage sequential design will be employed to conduct the trial for recurrent ependymoma.
* In the first stage, we will enroll 18 patients with RELA-fusion ependymoma and if 4 or more patients in Cohort 1 are progression free at 6 months, we will proceed to stage 2; otherwise, we will terminate the trial and conclude that marizomib is not effective.
* In the second stage, we will enroll 32 patients with non RELA-fusion ependymoma.
* Patients will be treated with marizomib in cycles consistent of 28 days until disease progression or a maximum of 24 cycles.

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

Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma

1. Biomedical Translational Research Information System (BTRIS): All IPD recorded in the medical record will be shared with intramural investigators upon request.
2. Database of Genotypes and Phenotypes (dbGaP): All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Progression was assessed by the Response assessment in neuro-oncology criteria (RANO) and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

To determine the safety of marizomib in recurrent ependymoma patients and in a subset of patients with more than 2 prior chemotherapies (RELA-fusion Cohort 2 and non-RELA-fusion Cohort 4).

To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by progression free disease after 6 months. Progression was assessed by the Response Assessment in Neuro-oncology (RANO) criteria and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Progression was assessed by the Response Assessment in Neuro-oncology criteria (RANO) and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom severity.To longitudinally evaluate participant reported outcome measures using self-reported symptom severity with daily activities using the MDASI-BT and/or MDASI-SP instrument.

To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by objective response. Complete Response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial Response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

Median amount of time subject survives 12 months after therapy

OS is defined as the time from treatment start date until date of death or date last known alive.

Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom interference.To longitudinally evaluate participant reported outcome measures using self-reported symptom interference with daily activities using the MDASI-BT and/or MDASI-SP instrument.

National Cancer Institute (NCI)

Marizomib at days 1, 8, and 15 of each 28-day cycle

Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total.

Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.

1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies

Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab	NCT02330562	Malignant Gliom... Glioblastoma	MRZ BEV	18 Years -	Celgene
Phase I Study of Marizomib + Panobinostat for Children With DIPG	NCT04341311	Diffuse Intrins... Pediatric Brain... Pediatric Brain... Pediatric Cance... Pediatric Brain... Diffuse Glioma	Marizomib Panobinostat	- 21 Years	Dana-Farber Cancer Institute
Expanded Access for Marizomib	NCT04644107	Solid Tumor	Marizomib	18 Years -	Celgene
Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma	NCT02103335	Multiple Myelom... Refractory Mult... Multiple Myelom...	pomalidomide marizomib low-dose dexame...	18 Years -	Celgene
Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma	NCT03727841	Anaplastic Epen... Ependymoma Ependymomas	Marizomib	-	National Institutes of Health Clinical Center (CC)
Marizomib Central Nervous System (CNS)	NCT05050305	Multiple Myelom... Multiple Myelom... Multiple Myelom...	Marizomib Pomalidomide Dexamethasone	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for marizomib

Every month we try and update this database with for marizomib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for marizomib

Every month we try and update this database with for marizomib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for marizomib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.