Hydrochloroquinine & Decitabine With Venetoclax in AML

Inclusion criteria

1\. Confirmed acute myeloid leukemia per 2022 WHO (≥20 % blasts or genetically-defined AML) 2. Age ≥ 18 years on the date of consent Disease status 3. Phase I: Relapsed/refractory (R/R) or newly-diagnosed, overy high risk defined as p53 mutation or secondary AML after MPN or chemotherapy/radiation exposure 4. An ECOG performance status of 0-2 5. Acceptable Organ function within 14 days of cycle 1 day 1 6. AST/ALT ≤ 3× ULN; total bilirubin ≤ 1.5× ULN (unless Gilbert's) 7. Creatinine clearance \> 60 mL/min (Cockcroft-Gault) 8. Subjects must have a baseline QTc interval of less than 450 milliseconds (\<450 ms) White blood cells \< 25 × 10⁹/L before first dose of hypomethylating agent - debulking with hydroxyurea/leukapheresis or up to 6 doses of cytarabine 100mg-200mg if needed is acceptable.

9\. HIV, HBV, and HCV patients are eligible if viral load is undetectable on stable therapy Wash-out from prior therapies should be ≥14 days from the last cytotoxic or targeted agent, and recovery to ≤Grade 1 non-hematologic toxicity 10. Reproductive precautions 11.Negative serum β-hCG for WOCBP; agreement to use highly effective contraception during treatment and ≥ 90 days after last dose Signed written informed consent and willingness to comply with study procedures

* Exclusion Criteria

  1. Leukemia subtype - Acute promyelocytic leukemia (APL, PML-RARA)
  2. CNS leukemia not cleared (\<5 WBC/µL \& no blasts), or symptomatic CNS involvement
  3. Recent or uncontrolled transplant-related complications Allogeneic HSCT ≤ 90 days before Day 1 Active grade ≥ 2 GVHD or systemic immunosuppression \>10 mg/day prednisone-equivalent
  4. Concurrent malignancies requiring active therapy. Any adequately treated in-situ cancers or those not expected to interfere with endpoints are allowed.
  5. Active, uncontrolled infection (bacterial, viral, or fungal) despite appropriate antimicrobial therapy
  6. Cardiac risk, NYHA class III/IV heart failure, unstable angina, recent MI (\< 6 months), clinically significant arrhythmia, Concomitant use of QT-prolonging medications that cannot be discontinued, or history of torsades de pointes
  7. Pregnant or breastfeeding.
  8. Patients with known G6PD deficiency.
  9. Investigational drug or major surgery within 28 days.
  10. Bleeding diathesis/coagulopathy that would preclude required marrow aspirates or lumbar puncture.
  11. Psychiatric or social condition that, in the investigator's judgment, would impair compliance with protocol-mandated visits/procedures.