Can a pill and injection combo beat AML without harsh chemo?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria Patients must satisfy ALL of the following criteria to be eligible for enrolment: 1. Age 18-50 years (inclusive) at the time of enrolment 2. Confirmed diagnosis of AML (non-APL) per WHO 2022 Classification: ≥20% blasts in bone marrow or peripheral blood, or documented leukaemia-defining cytogenetic abnormality regardless of blast count (e.g. t(8;21), inv(16), t(15;17) is excluded as APL). Diagnosis must be confirmed by bone marrow aspirate and/or biopsy with morphology, flow cytometry, and cytogenetics. 3. Newly diagnosed AML: no prior cytotoxic therapy for AML (excluding hydroxyurea for blast cytoreduction, which is permitted for ≤7 days prior to enrolment) 4. ECOG Performance Status 0-2 5. Adequate end-organ function at screening (within 7 days of first study drug administration): 1. Serum creatinine ≤2 × ULN or CrCl ≥40 mL/min (CKD-EPI formula) 2. ALT and AST ≤3 × ULN (≤5 × ULN if attributed to hepatic leukaemic infiltration) 3. Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert syndrome or hepatic leukaemic infiltration) 4. LVEF ≥45% by echocardiography or MUGA (assessed within 28 days of enrolment) 6. Willing and able to provide written informed consent (patient or legally authorised representative for patients with AMS at presentation) 7. Willingness to comply with all study procedures, including bone marrow assessments, follow-up visits, and MRD monitoring 8. For women of childbearing potential (WOCBP): negative serum or urine pregnancy test within 72 hours of Cycle 1 Day 1, and agreement to use effective contraception throughout study treatment and for 12 months after last dose 9. For male patients with female partners of childbearing potential: agreement to use effective contraception and refrain from sperm donation throughout treatment and for 6 months after last dose 5.2 Exclusion Criteria Patients will be excluded from participation if ANY of the following apply: 10. Acute promyelocytic leukaemia (APL) \[t(15;17); PML-RARA\]: patients with APL must be referred for ATRA-based therapy as per institutional standard 11. AML secondary to myeloproliferative neoplasm (MPN) in blast phase, where prior MPN was treated with ruxolitinib within 8 weeks of enrolment (due to drug interaction potential with venetoclax) 12. Prior exposure to a BCL-2 inhibitor (venetoclax, navitoclax, or other) at any time 13. Prior exposure to HMA therapy (azacitidine or decitabine) for a pre-existing MDS or MPN within 6 months of AML diagnosis 14. Active, uncontrolled systemic infection at the time of enrolment that in the investigator's judgement would preclude initiation of cytotoxic therapy (note: controlled infection with appropriate antimicrobial therapy is not an exclusion) 15. Known active hepatitis B virus (HBV) infection (HBsAg positive) without established antiviral prophylaxis; or active hepatitis C virus (HCV) infection with detectable viral load 16. Known HIV infection with CD4 count \<350 cells/μL or detectable viral load (HIV-positive patients with well-controlled disease on antiretroviral therapy may be enrolled after discussion with the Principal Investigator and Infectious Disease consultant) 17. Cardiac exclusions: 1. QTcF \>480 ms on screening ECG 2. Clinically significant and uncontrolled arrhythmia 3. NYHA Class III-IV heart failure 4. Acute coronary syndrome or stroke within 6 months of enrolment 18. Malabsorption syndrome or other gastrointestinal condition that would significantly impair oral absorption of venetoclax 19. Concomitant strong CYP3A4 inhibitors (e.g. ketoconazole, posaconazole, voriconazole, clarithromycin) or inducers (e.g. rifampicin, phenytoin, carbamazepine) that cannot be safely discontinued or dose-adjusted. (Note: azole antifungals require venetoclax dose reduction per label - see Section 7.4) 20. Concurrent active malignancy requiring systemic therapy (patients with adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix are eligible) 21. Pregnancy or breastfeeding 22. Participation in any other interventional clinical trial within 4 weeks of enrolment 23. Any condition that, in the investigator's judgement, would compromise patient safety, protocol compliance, or the integrity of study data