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

Phase 2RecruitingNCT07451912

The First Affiliated Hospital of Soochow University29 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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).

Secondary Outcomes

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) 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).

Time frame: 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

Proportion of participants with MRD \<1×10-⁴ detected by flow cytometry after treatment.

Time frame: 21 to 28 days after the end of every treatment

Duration of Remission (DOR)

If no relapse or death occurs during follow-up, DOR is censored at the last follow-up date.

Time frame: 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 during the study period.

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).

Overall Survival (OS)

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.

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).