Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS

Exclusion Criteria

• •1. Age ≥75 years Or
• •2. Age ≥18 years with at least one of the following comorbidities:
• •3. Significant heart or lung comorbidities, as reflected by at least one of the following:
• •4. Left ventricular ejection fraction (LVEF) ≤50%
• •5. Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
• •6. Forced expiratory volume in 1 second (FEV1) ≤65% of expected
• •7. Chronic stable angina or congestive heart failure controlled with medication
• •8. Other comorbidity or conditions that the Investigator judges as incompatible with intensive chemotherapy, which must be documented
• •9. ECOG=2
• •6. Creatinine clearance (estimated by the Modification of Diet in Renal Disease (MDRD) equation or measured by 24 hours urine collection) ≥45 mL/min
• •7. Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN), unless attributed to leukemia (in AML patients)
• •8. Total bilirubin ≤3 XULN unless due to Gilbert disease
• •9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• •10. Women of reproductive potential must have a negative serum pregnancy test within 48 hours prior to the first day of any BST-236 treatment course
• •11. Women of reproductive potential must use two forms of effective birth control methods starting from at least 1 month prior to BST-236 first dose and until 3 months following the last BST-236 administration day (acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptives, or double-barrier method condom or diaphragm with spermicide)
• •12. Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 3 months following the last dose of study drug
• •13. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
• •14. Patient must be able to adhere to the study visit schedule and other protocol requirements
• •1. MDS or AML evolving from a pre-existing myeloproliferative neoplasm (MPN)
• •2. MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
• •3. Acute promyelocytic leukemia
• •4. Previous treatment for AML or MDS with drugs other than HMA or LDAC or combinations of venetoclax with either HMA or LDAC
• •5. Previous allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation
• •6. Participation in a previous clinical trial involving use of an investigational drug within 30 days or at least 5 half-lives of tested drug (whichever is shorter) of study day 1
• •7. Peripheral White Blood Cell (WBC) count \>30,000 /µL in the 48 hours prior to first BST-236 dose administration. Hydroxyurea administration or leukapheresis is permitted to meet this criterion
• •8. Administration of HMA, LDAC, or venetoclax within 14 days prior to Study Day 1
• •9. Previous treatment with cytarabine at a dose higher than 20 mg/ m2/d
• •10. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
• •11. Any medical or surgical condition, presence of laboratory abnormalities or psychiatric illness that may preclude safe and complete study participation based on the Investigator's judgment
• •12. Diagnosis of malignant disease (other than AML) within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma, or other local malignancy excised or irradiated with a high probability of cure and not treated with systemic or topical chemotherapy)
• •13. Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to first BST-236 dose administration
• •14. History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
• •15. Life expectancy shorter than 3 months attributed to any known medical condition other than AML/MDS
• •16. In 12 leads ECG, corrected QT interval (QTc)\>480msec or history of QT prolongation or Torsades de pointes