Venetoclax plus a short (3-day) decitabine schedule for untreated elderly or unfit adults with AML

Efficacy and Safety of Venetoclax Plus Decitabine in Elderly/Unfit Patients With Newly Diagnosed AML: A Multicenter Single-Arm Study

This trial will see if venetoclax combined with a short (3-day) decitabine course helps people with newly diagnosed AML who are elderly or cannot receive standard chemotherapy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 65 Years and up
• Sex: All
• Sponsor: The Second Hospital of Hebei Medical University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Hebei)
• Trial ID: NCT07117422 on ClinicalTrials.gov

What this trial studies

This interventional study gives treatment‑naïve adults with AML who are elderly or ineligible for standard chemotherapy a combination of venetoclax and a shortened 3‑day decitabine regimen. Participants are treated at The Second Hospital of Hebei Medical University and a collaborating hospital in Hebei province and are followed closely for response, measurable residual disease (MRD) status, survival, and side effects. The main outcomes include remission rates, MRD negativity, tolerability, and overall survival, with additional monitoring for duration of response and treatment‑related toxicity. The protocol adapts existing venetoclax plus hypomethylating agent approaches to a condensed decitabine schedule aiming to improve efficacy and reduce prolonged toxicity in this frail population.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed AML who are age ≥65 and choose not to have intensive chemotherapy or adults >18 who are judged ineligible for standard‑dose chemotherapy because of poor performance status, cardiac or pulmonary impairment, reduced kidney function (CrCl 30–45 mL/min), or other contraindications to intensive treatment.

Not a fit: Patients who are fit for standard intensive chemotherapy, those with acute promyelocytic leukemia (APL) or certain excluded AML subtypes, or those who do not meet the organ‑function criteria are not expected to benefit from or be eligible for this regimen.

Why it matters

Potential benefit: If successful, this approach could raise complete remission and MRD‑negative rates while improving tolerability and extending survival for elderly or unfit patients with newly diagnosed AML.

How similar studies have performed: Prior studies have shown that venetoclax combined with hypomethylating agents improves response and survival in elderly/unfit AML, while the specific 3‑day decitabine schedule is a more recent, relatively novel approach still being tested for improved efficacy and tolerability.

Eligibility criteria

Inclusion Criteria:

1. Patients meeting the World Health Organization (WHO) 2022 diagnostic criteria for acute myeloid leukemia (AML), excluding:Acute promyelocytic leukemia (APL)

   AML with recurrent genetic abnormalities, including:t(8;21)(RUNX1::RUNX1T1)

   inv(16)(p13.1q22) or t(16;16)(p13.1q22)/CBFβ::MYH11
2. Patients classified as AML, not otherwise specified (NOS) per WHO criteria, excluding:Acute panmyelosis with myelofibrosis 、Myeloid sarcoma
3. Age and fitness criteria:

   -Group A: Age ≥65 years (unwilling to receive intensive chemotherapy)

   Group B: Age \>18 years and ineligible for standard-dose chemotherapy, defined by ≥1 of the following:ECOG performance status 2 or 3；History of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% DLCO ≤65% or FEV1 ≤65%Creatinine clearance ≥30 mL/min but ≤45 mL/min (Cockcroft-Gault or 24-hour urine collection)、Any other condition deemed incompatible with standard chemotherapy (requires PI approval)
4. No prior AML therapy, except:Hydroxyurea、Low-dose cytarabine (\<1.0 g/day)
5. ECOG performance status ≤3
6. Laboratory requirements (within 7 days prior to treatment):AST/ALT/ALP ≤3×ULN (≤5×ULN if due to leukemic involvement)、Total bilirubin ≤2×ULN、Cardiac enzymes \<2×ULN、Serum creatinine clearance ≥30 mL/min (measured or calculated)
7. Contraception requirements:Negative pregnancy test (within 72 hours before treatment) for women of childbearing potential；Agreement to use effective contraception during treatment and for 3 years after therapy
8. Life expectancy ≥2 months
9. Informed consent:Signed by patient, legal guardian, or immediate family member (if patient is unable to consent due to medical condition)

Exclusion Criteria:

1. AML with BCR::ABL1 fusion or chronic myeloid leukemia (CML) in blast crisis.
2. Previously treated AML patients (received prior induction chemotherapy, regardless of response).
3. Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN)
4. Concurrent hematologic disorders (e.g., hemophilia, myelofibrosis, or other conditions deemed ineligible by the investigator). Exception: Patients with prior blood count abnormalities but confirmed non-MDS/MPN by bone marrow examination may be included.
5. Pregnant or lactating women.
6. Hypersensitivity to any study drugs.
7. Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation.
8. Active malignancy in other organs (requiring treatment).
9. Clinically significant hepatic/renal dysfunction exceeding inclusion criteria limits.
10. Active cardiac disease, defined as ≥1 of the following:Myocardial infarction within 6 months before enrollment；History of symptomatic arrhythmia requiring medication；Uncontrolled/symptomatic congestive heart failure (NYHA Class \>2)
11. Active infections, including:Untreated tuberculosis or pulmonary aspergillosis

    Known HIV, active hepatitis B (HBV), or hepatitis C (HCV)
12. Central nervous system (CNS) leukemia at baseline.
13. Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance
14. Conditions limiting oral drug absorption (e.g., malabsorption syndrome).
15. Investigator's discretion for ineligibility.

Where this trial is running

Hebei

• The Second Hospital of Hebei Medical University — Hebei, China (Recruiting)

Study contacts

• Principal investigator: Ling Xi Guo — The Second Hospital of Hebei Medical University
• Study coordinator: Ling Xi Guo

Conditions AML, Adult