Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

Eligibility Criteria

• * WBC must be less than 25,000/ul prior to study start (hydroxyurea allowed).
• * A bone marrow aspirate must be performed, and tissue collected for entrance to the trial unless circulating blasts \>/= 5% in which case, peripheral blood can be used.
• * Eastern Cooperative Oncology Group Performance Status of 0 - 2.
• * Must have adequate hepatic and renal function as demonstrated by the following:
• * Anticancer therapy, including investigational agents \</= 2 weeks or \</= 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted).
• * Inadequate recovery from toxicity attributed to prior anti-cancer therapy to \</= Grade 1 (NCI CTCAE v5.0), excluding alopecia or fatigue.
• * Prior treatment with SINE compounds or other inhibitors of XPO1.
• * History of allogeneic hematopoietic stem cell transplant (HCT), or other cellular therapy product, within 3 months.
• * Active acute or chronic GVHD requiring calcineurin inhibitors or steroid dosing \>/= 10mg/day or patients within 4 weeks of stopping calcineurin inhibitors for GVHD.
• * Radiation therapy or major surgery within 3 weeks.
• * Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis, even if parenteral, is acceptable.
• * Inability to swallow oral medications.
• * Active documented central nervous system leukemia.
• * Second active malignancy within past 2 years except for basal or squamous cell carcinoma of the skin, ductal carcinoma of breast in situ or cervical carcinoma in situ.
• * Women of childbearing age or potential must have negative pregnancy test and must not be actively breastfeeding to enroll on the study
• * Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator.
• * Any condition not listed but deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents.