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

NCT07451912 | Recruiting Phase 1

• 1 other identifier: SZAML-05
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.How well does this treatment combination prevent the disease from coming back (relapse-free survival)?
2. 2.What percentage of participants achieve a good response (complete remission or complete remission with incomplete blood cell recovery) after 2 treatment cycles?
3. 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?
4. 4.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.
5. 5.If they respond well to induction treatment, move to a "consolidation phase" and receive at least 4 more cycles of the same treatment combination.
6. 6.Have regular check-ups during treatment (like blood tests, bone marrow tests, and heart checks) to monitor treatment response and side effects.
7. 7.Be followed up for 2 years after treatment ends to check if the disease comes back and their overall health.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS)

  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 Outcomes (5)

• Composite Remission Rate after 2 Induction Cycles

  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

  21 to 28 days after the end of every treatment

• Duration of Remission (DOR)

  From date of achieving CR/CRi until first occurrence of disease relapse or death from any cause, assessed up to 60 months.

• Relapse Rate

  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)

  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).

Study Arms (1)

Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients)

EXPERIMENTAL

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)

Interventions

Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients) DRUG

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

Venetoclax + Hypomethylating Agents + Low-Dose Cytarabine for CEBPA-Mutated AML (Unfit Patients)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients can participate in this study only if they meet all the following enrollment criteria:
• Aged over 18 years, male, or female who is neither pregnant nor lactating;
• Newly diagnosed acute myeloid leukemia (AML) with CEBPA mutation;
• ECOG performance status ≤ Grade 3;
• Capable of understanding and willing to participate in the study, and able to sign the informed consent form;
• 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.

You may not qualify if:

• Pregnant or lactating women;
• 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);
• 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;
• Other conditions judged by the investigator to make the patient unfit for participating in this study.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Suning Chen

CONTACT

008613814881746; chensuning@sina.com

Wenzhi Cai

CONTACT

008615106202752

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: March 5, 2026
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CN (1)