8-Chloroadenosine in Combination With Venetoclax for the Treatment of Patients With Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative.

• Age: >= 18 years.

• Eastern Cooperative Oncology Group (ECOG) =< 2.

• Life expectancy > 3 months.

• Patients with histologically confirmed acute myeloid leukemia (AML), according toWorld Health Organization (WHO) criteria, with relapsed/refractory disease.

• Patients must have any one of the following treatment history criteria:

• Relapsed AML

• Failed at least 1 line of salvage therapy or

• Untreated relapse and are not candidates for allogeneic hematopoietic stemcell transplantation (alloHCT)

• De novo AML

• have not achieved complete response (CR) after 2 lines of therapy or

• refractory to frontline therapy and not eligible for alloHCT

• AML evolving from myelodysplastic syndrome (MDS) or myeloproliferative disorderwho have failed hypomethylating agents (HMA) or induction chemotherapy

• Patients who have relapsed after allo-HCT are eligible if they are at least 3months after HCT, do not have active graft versus host disease (GVHD) and areoff immunosuppression except for maintenance dose of steroids (prednisone 10mg/day or less).

• Male subjects must agree to not donate sperm while taking protocol therapy throughat least 90 days after the last dose.

• White blood cell (WBC) =< 25 x 10^9/L prior to initiation of venetoclax.Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may berequired.

• Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease).

• Aspartate aminotransferase (AST) =< 2.5 x ULN.

• Alanine aminotransferase (ALT) =< 2.5 x ULN.

• Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gaultformula.

• QTc =< 480 ms.

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. Ifthe urine test is positive or cannot be confirmed as negative, a serum pregnancytest will be required.

• Agreement by females and males of childbearing potential* to use an effective methodof birth control or abstain from heterosexual activity for the course of the studythrough at least 6 months (females) and 3 months (males) after the last dose ofprotocol therapy.

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only).

Exclusion Criteria:

• Current or planned use of other investigational agents, antineoplastic, biological,chemotherapy, or radiation therapy during the study treatment period, or within 2weeks prior to day 1 of protocol therapy, with the following exception:

• Hydroxyurea which may be continued through cycle 1.

• Expected to undergo HCT within 120 days of enrollment.

• Current or planned use of agents that prolong or suspected to prolong QTc.

• Received strong or moderate CYP3A inducers or St. John's Wort within 7 days prior today 1 of protocol therapy.

• Received strong or moderate CYP3A inhibitors, or consumed grapefruit, grapefruitproducts, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to day 1 of protocol therapy.

• P-glycoprotein (P-gp) inhibitors within 7 days prior to day 1 of protocol therapy.

• Narrow therapeutic index P-gp substrates within 7 days prior to day 1 of protocoltherapy.

• Acute promyelocytic leukemia.

• Active central nervous system (CNS) leukemia.

• Active fungal infection or bacterial sepsis.

• Class III/IV cardiovascular disability according to the New York Heart Associationclassification.

• Participants with clinically significant arrhythmia or arrhythmias not stable onmedical management within two weeks of enrollment. Subjects with controlled,asymptomatic atrial fibrillation can enroll.

• History of acute cardiovascular ischemic event, i.e., myocardial infarction orunstable angina within 6 months of enrollment.

• History of unexplained syncope, significant histories of CAD (requiringrevascularization by percutaneous coronary intervention [PCI] or coronary arterybypass grafting [CABG]), cardiomyopathy (ejection fraction [EF] < 50%).

• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g.,gastric bypass surgery, gastrectomy).

• Unable to swallow capsules, has a partial or small bowel obstruction, or has agastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowelresection with malabsorption).

• Active peptic ulcer disease.

• Other active malignancy except for localized skin cancer, bladder, prostate, breastor cervical carcinoma in situ.

• Females only: Pregnant or breastfeeding.

• Any other condition that would, in the Investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures.

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics).