Marizomib Central Nervous System (CNS)

Exclusion Criteria

• •Prior exposure to marizomib. and primary refractoriness to pomalidomide or a pomalidomide combination. Prior pomalidomide exposure is permitted but patients must have shown tolerance (defined as no grade 3 or greater non-hematologic toxicity), as well as responsiveness to pomalidomide-based therapy (defined as MR or better).
• •Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy/watchful waiting.
• •Known GI disease or GI procedure that could interfere with the oral absorption of pomalidomide including difficulty swallowing.
• •Systemic treatment, within 14 days before the first dose of pomalidomide, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
• •Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination during the screening period.
• •Any medical or psychiatric illness that in the investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
• •Current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within the past 6 months.
• •The following therapies within the stated time frames prior to initiation of therapy: previous cytotoxic therapies, including cytotoxic investigational agents, for MM within 3 weeks; IMiDs, PIs, corticosteroids, other approved therapeutics and monoclonal antibodies (Mabs) within 2 weeks; and investigational therapies within 4 weeks. Please note consideration of the interval for investigational agents from already approved classes of drug in MM (e.g. Cell-Mods, Mabs) can be considered on a case by case basis with the PI. Prior peripheral stem cell transplant within 12 weeks and the use of live vaccines within 30 days.
• •Prior allogeneic stem cell transplantation with active graft-versus-host-disease (grade 2 or greater).
• •Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
• •Daily requirement for corticosteroids equivalent to \> 10 mg/day prednisone, except for inhalation corticosteroids, for the RRMM cohort. For patients with CNS involvement who require a higher dose of corticosteroids for control of vasogenic edema (e.g. 16 mg/day dexamethasone), eligibility will be determined on a case-by-case basis after discussion with the PI.
• •Any \> Grade 1 adverse reaction unresolved from previous treatments according to the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTC AE v.5.0). The presence of alopecia any grade or peripheral neuropathy ≤ Grade 2 without pain is allowed.
• •Concurrent symptomatic amyloidosis or plasma cell leukemia.
• •POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
• •Known active infection requiring parenteral or oral anti-infective treatment within 7 days of start of therapy.
• •Known human immunodeficiency virus or active hepatitis C viral infection.
• •Active hepatitis B viral infection (defined as HBsAg+).
• •* Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
• •* Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation.
• •Pregnant or breast-feeding females.
• •Participants who are receiving any other investigational agents.
• •History of erythema multiforme or severe hypersensitivity to prior IMiD's®.
• •Inability to tolerate thromboprophylaxis.
• •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.
• •Known hypersensitivity to thalidomide or lenalidomide or other drugs included in this study.
• •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drugs.
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