Venetoclax with hypomethylating drugs and low-dose cytarabine for adults with CEBPA‑mutated AML who can't tolerate intensive chemotherapy

Prospective Multicenter Clinical Study of Venetoclax Combined With Hypomethylating Agents and Subcutaneous Cytarabine in Induction Therapy for CEBPA-Mutated Acute Myeloid Leukemia

This trial will try combining venetoclax with azacitidine or decitabine plus low‑dose cytarabine to treat adults newly diagnosed with CEBPA‑mutated AML who are unfit for intensive chemotherapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07451912 on ClinicalTrials.gov

What this trial studies

This phase 1/2, single‑center study gives adults with newly diagnosed CEBPA‑mutated AML who are judged unfit for intensive chemotherapy two cycles of induction therapy combining oral venetoclax with a hypomethylating agent (azacitidine or decitabine) plus subcutaneous low‑dose cytarabine. The phase 1 portion focuses on establishing safe dosing and tolerability, and the phase 2 portion expands to measure efficacy signals. Primary outcomes include relapse‑free survival, rate of complete remission or complete remission with incomplete blood count recovery (CR/CRi) after two cycles, MRD negativity, and treatment‑related adverse events. The protocol also includes exploratory analyses to track how the disease may evolve at relapse.

Who should consider this trial

Good fit: Adults (≥18 years) with newly diagnosed CEBPA‑mutated AML who are judged 'unfit' for intensive chemotherapy (for example advanced age, severe comorbidities, active infection, cognitive impairment, or persistent ECOG ≥3) and who can provide informed consent are ideal candidates.

Not a fit: Patients who are fit for intensive chemotherapy, lack a CEBPA mutation, are pregnant or lactating, or have uncontrolled organ dysfunction or other exclusions are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this lower‑intensity combination could increase remission rates and prolong relapse‑free survival for patients with CEBPA‑mutated AML who cannot receive intensive chemotherapy.

How similar studies have performed: Combinations of venetoclax with hypomethylating agents have shown strong activity in older or unfit AML populations, but specific data for CEBPA‑mutated disease and for the addition of low‑dose cytarabine are limited.

Eligibility criteria

Inclusion Criteria:

* Patients can participate in this study only if they meet all the following enrollment criteria:

  1. Aged over 18 years, male, or female who is neither pregnant nor lactating;
  2. Newly diagnosed acute myeloid leukemia (AML) with CEBPA mutation;
  3. ECOG performance status ≤ Grade 3;
  4. Capable of understanding and willing to participate in the study, and able to sign the informed consent form;
  5. Patients are judged as "unfit" according to the Ferrara criteria. A patient is considered "unfit" if they meet at least one of the following criteria:

     * Advanced age: \> 75 years old;

       * Presence of severe underlying comorbidities involving the heart, lungs, kidneys, or liver; ③ Presence of active infection unresponsive to anti-infective treatment;

         * Presence of cognitive impairment; ⑤ Poor performance status (persistent ECOG score ≥ Grade 3); ⑥ Other comorbidities judged by the investigator to make the patient unfit for intensive chemotherapy.

Exclusion Criteria:

* Patients are not suitable for participating in this study if they meet any of the following exclusion criteria:

  1. Pregnant or lactating women;
  2. Previous receipt of chemotherapy or targeted drug therapy for leukemia before the study treatment (except oral hydroxyurea used to reduce white blood cell count and/or leukapheresis);
  3. As known to the participant and the investigator, the participant may be unable to complete all study visits or procedures required by the study protocol (including follow-up visits) and/or unable to comply with the required study procedures;
  4. Other conditions judged by the investigator to make the patient unfit for participating in this study.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Suning Chen

Conditions Acute Myeloid Leukemia; CEBPA Mutation; Unfit, New-diagnosis AML