Efficacy and Safety of BST-236 in Newly Diagnosed Acute Myeloid Leukemia Patients, Unfit for Standard Induction Therapy

Inclusion Criteria:

Adult ≥18 years of age

AML according to the 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: ≥20% blasts in peripheral blood or marrow

de-novo AML or
AML secondary to MDS or
AML secondary to exposure to potentially leukemogenic therapies or agents (e.g. radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 2 years

Not eligible for standard induction chemotherapy;

Age ≥75 years or
Age ≥18 years with at least one of the following comorbidities:

i. Clinically significant heart or lung comorbidities, as reflected by at least one of:

Left ventricular ejection fraction (LVEF) ≤50%
Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected
Forced expiratory volume in 1 second (FEV1) ≤65% of expected ii. Chronic stable angina or congestive heart failure controlled with medication iii. Other contraindication(s) to anthracycline therapy (must be documented) iv. Other comorbidity that the Investigator judges as incompatible with intensive remission induction chemotherapy, which must be documented
Creatinine clearance (estimated by the Cockroft-Gault (C-G) or measured by 24 hours urine collection) ≥45 mL/min
Liver enzymes (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal (ULN)
Total bilirubin ≤1.5 x ULN unless due to known history of Gilbert's disease
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
Prepared and able to give written (signed and dated) informed consent, which includes compliance with study requirements and restrictions prior to admission to the study
Women of reproductive potential must have a negative serum pregnancy test within 48 hours of the first day of any BST-236 treatment course
Women or men of reproductive potential must use (or have his/her partner use) two forms of effective birth control methods starting from 1 month prior to screening 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, partner's vasectomy, or double-barrier method condom or diaphragm with spermicide)
Patient must voluntarily sign and date an ICF, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
Patient must be able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

Patient has relapsed or refractory AML
Patient has acute promyelocytic leukemia
Any previous treatment for AML (except for hydroxyurea or up to one treatment course with hypomethylating agents (HMA))
Patient has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation
Previous use (prior to study initiation) of drugs containing cytarabine as an active ingredient
Use of any HMA for the treatment of MDS within 30 days of study Day 1
Participation in a previous clinical trial and/or use of an investigational drug within 90 days or at least 5 half-lives of tested drug (whichever is longer) of initial screening assessment
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
Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
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
Diagnosis of malignant disease 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 chemotherapy)
Active malignant disease other than AML
Leptomeningeal/central nervous system involvement of AML
Myeloid sarcoma as a sole manifestation of AML
Surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) in the 14 days prior to BST-236 administration
Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 4 congestive heart failure
Shortness of breath requiring continuous oxygen treatment for at least 15 hours per day in chronically hypoxemic patients
History of allergic reactions attributed to compounds of similar chemical composition as BST-236 and/or cytarabine
Life expectancy shorter than 3 months attributed to any known medical condition other than AML
Active/chronic Hepatitis B Virus (HBV) infection (based on positive surface antigen (HBsAg)), Hepatitis C Virus (HCV) infection (HCV) (based on positive HCV antibody (Ab)), or Human Immunodeficiency Virus (HIV)-1 or HIV-2 (based on positive HIV antibody)