Eltanexor and Venetoclax for the Treatment of Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

Inclusion Criteria

• Age ≥ 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and must be able to meet all study requirements
• For MDS: Morphologically confirmed diagnosis of MDS with increased blasts (>/= 5%), with a prior DNA methyltransferase inhibitor (DNMTi) treatment and progression after 2 cycles or stable disease after 4 cycles
• For AML: Morphologically confirmed diagnosis of AML in accordance with World Health Organization (WHO) diagnostic criteria that is relapsed or refractory following ≥ 1 line(s) of therapy
• White blood cells (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
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and/or aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3x upper limit of normal (ULN)
• Direct bilirubin ≤ 1.5 x ULN or ≤ 2.5x ULN (known Gilbert’s Syndrome as cause of elevated bilirubin is allowed)
• Calculated creatinine clearance >50 ml/min (per the Cockroft-Gault formula)
• Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications

Exclusion Criteria

• Anticancer therapy, including investigational agents ≤ 2 weeks or ≤ 5 half-lives of the drug, whichever is shorter, prior to cycle 1 day 1 (C1D1). (Use of hydroxyurea is permitted)
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy to ≤ grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v] 5.0), excluding alopecia or fatigue
• Prior treatment with SINE compounds (XPO1 inhibitors)
• History of allogeneic hematopoietic stem cell transplant (HCT), or other cellular therapy product, within 3 months
• Active acute or chronic graft versus host disease (GVHD) requiring calcineurin inhibitors or steroid dosing ≥ 10 mg/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 tolerate oral medication
• 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 within 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