Venetoclax Plus Hypomethylating Agents and Subcutaneous Cytarabine for CEBPA-Mutated AML

March 4, 2026 updated by: Chen Suning, The First Affiliated Hospital of Soochow University

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

The goal of this clinical trial is to learn if a treatment combination-venetoclax plus hypomethylating agents (like azacitidine or decitabine) and low-dose cytarabine-works to treat adults with newly diagnosed CEBPA-mutated acute myeloid leukemia (AML) who can't tolerate intensive chemotherapy. It will also check how safe this treatment combination is and explore how the disease might change if it comes back. The main questions it aims to answer are:

  1. How well does this treatment combination prevent the disease from coming back (relapse-free survival)?
  2. What percentage of participants achieve a good response (complete remission or complete remission with incomplete blood cell recovery) after 2 treatment cycles?
  3. What percentage of participants have no detectable remaining leukemia cells (measurable residual disease, MRD) after treatment? What side effects do participants have, and how serious are these side effects?

Participants will:

  1. First, go through a 2-cycle "induction phase": Take venetoclax by mouth (100mg on day 1, 200mg on day 2, 400mg from day 3 to day 28), get hypomethylating agents (azacitidine injected under the skin or decitabine injected into a vein), and low-dose cytarabine (injected under the skin) as planned.
  2. If they respond well to induction treatment, move to a "consolidation phase" and receive at least 4 more cycles of the same treatment combination.
  3. Have regular check-ups during treatment (like blood tests, bone marrow tests, and heart checks) to monitor treatment response and side effects.
  4. Be followed up for 2 years after treatment ends to check if the disease comes back and their overall health.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

29

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Wenzhi Cai
  • Phone Number: 008615106202752

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215006
        • Recruiting
        • The First Affiliated Hospital of Soochow University
        • Contact:
          • The First Affiliated Hospital of Soochow University
          • Phone Number: 0086-0512-67972861
          • Email: sdfyec@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients)

  1. Induction Therapy (2 Cycles in Total) All medications are administered in a 28-day cycle; the second cycle is given regardless of the response to the first cycle.

    Medication Generic Name Dosage Form Dosage Administration Frequency Duration per Cycle Venetoclax Oral tablets 100 mg on Day 1; 200 mg on Day 2; 400 mg from Day 3 to Day 28 Once daily (oral) Days 1-28 Azacitidine (alternative to decitabine) Injectable 75 mg/m² per day Once daily (subcutaneous injection) Days 1-7 Decitabine (alternative to azacitidine) Injectable 20 mg/m² per day Once daily (intravenous injection) Days 1-5 Cytarabine (low-dose) Injectable 20 mg/m² per day Once daily (subcutaneous injection) Days 1-10

  2. Consolidation Therapy (At Least 4 Cycles) Same as the therapy of induction
Drug: Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients)

  1. Induction Therapy (2 Cycles in Total) All medications are administered in a 28-day cycle; the second cycle is given regardless of the response to the first cycle.

    Medication Generic Name Dosage Form Dosage Administration Frequency Duration per Cycle Venetoclax Oral tablets 100 mg on Day 1; 200 mg on Day 2; 400 mg from Day 3 to Day 28 Once daily (oral) Days 1-28 Azacitidine (alternative to decitabine) Injectable 75 mg/m² per day Once daily (subcutaneous injection) Days 1-7 Decitabine (alternative to azacitidine) Injectable 20 mg/m² per day Once daily (intravenous injection) Days 1-5 Cytarabine (low-dose) Injectable 20 mg/m² per day Once daily (subcutaneous injection) Days 1-10

  2. Consolidation Therapy (At Least 4 Cycles) Same as the therapy of induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-Free Survival (RFS)
Time Frame: From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).
Defined as the time from the date of achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) to the first occurrence of disease relapse (reappearance of ≥5% blasts in the bone marrow, presence of blasts in the peripheral blood, or new extramedullary disease) or death from any cause, whichever comes first. For participants who remain in remission at the end of the follow-up period, RFS is censored at the date of the last confirmed remission assessment.
From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Remission Rate after 2 Induction Cycles
Time Frame: Proportion of participants who achieve CR or CRi after completing 2 cycles of induction therapy. (Each cycle is 28 days)

Proportion of participants who achieve CR or CRi after completing 2 cycles of induction therapy. (Each cycle is 28 days) CR: Defined by the following criteria simultaneously: bone marrow blasts <5%, no blasts in the peripheral blood, absolute neutrophil count >1.0×10⁹/L, platelet count >100×10⁹/L, no extramedullary infiltration, and no relapse within 4 weeks.

CRi: Meets all CR criteria except for incomplete hematologic recovery (absolute neutrophil count ≤1.0×10⁹/L or platelet count ≤100×10⁹/L).
Proportion of participants who achieve CR or CRi after completing 2 cycles of induction therapy. (Each cycle is 28 days)
Minimal Residual Disease (MRD) Negativity Rate
Time Frame: 21 to 28 days after the end of every treatment
Proportion of participants with MRD <1×10-⁴ detected by flow cytometry after treatment.
21 to 28 days after the end of every treatment
Duration of Remission (DOR)
Time Frame: From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 60 months.
If no relapse or death occurs during follow-up, DOR is censored at the last follow-up date.
From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 60 months.
Relapse Rate
Time Frame: Proportion of participants who experience disease relapse after achieving CR/CRi, assessed up to 48 months (2 years after the last patient has been enrolled into the study).
Proportion of participants who experience disease relapse after achieving CR/CRi during the study period.
Proportion of participants who experience disease relapse after achieving CR/CRi, assessed up to 48 months (2 years after the last patient has been enrolled into the study).
Overall Survival (OS)
Time Frame: From start of treatment until death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).
Time from the start of treatment to death from any cause. For participants who remain alive at the end of the follow-up period, OS is censored at the date of the last survival confirmation.
From start of treatment until death from any cause, assessed up to 48 months (2 years after the last patient has been enrolled into the study).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Soochow University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

December 15, 2025

First Submitted That Met QC Criteria

March 4, 2026

First Posted (Actual)

March 5, 2026

Study Record Updates

Last Update Posted (Actual)

March 5, 2026

Last Update Submitted That Met QC Criteria

March 4, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SZAML-05

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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