Venetoclax, Chidamide, and Chiglitazar Sodium (VCC) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This is a multicenter, prospective, single-arm clinical study evaluating the efficacy and safety of venetoclax, chidamide, and chiglitazar sodium (VCC) in patients with relapsed or refractory acute myeloid leukemia (R/R AML). Participants will receive VCC combination therapy according to the study protocol. The primary objective is to evaluate the antileukemic efficacy of the VCC regimen, while safety and tolerability will also be assessed throughout the study.

• venetoclax, chidamide, and chiglitazar sodium (VCC) (Drug): Participants will receive oral chidamide 30 mg twice weekly for 2 weeks, venetoclax 200 mg once daily for 2 weeks, and chiglitazar sodium 48 mg once daily on Days 1-28 of each 28-day cycle. At least two cycles will be administered. Dose modifications are permitted according to clinical condition, laboratory findings, adverse events, and venetoclax plasma concentrations.

Primary outcomes

• Composite Complete Remission Rate (CR + CRi) [Up to 12 months]: The proportion of participants who achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following VCC treatment. Treatment response will be assessed according to the response criteria specified in the study protocol.

Secondary outcomes

• 1-Year Progression-Free Survival (PFS) [Up to 12 months]: The proportion of participants who are alive without disease progression at 1 year after initiation of VCC treatment. Progression-free survival is defined as the time from initiation of study treatment to disease progression or death from any cause, whichever occurs first.
• 1-Year Overall Survival (OS) [Up to 12 months]: The proportion of participants who are alive at 1 year after initiation of VCC treatment. Overall survival is defined as the time from initiation of study treatment to death from any cause.
• Change in Health-Related Quality of Life Assessed by EQ-5D-5L [Up to 24 months]: Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Changes in patient-reported health status during treatment will be evaluated relative to baseline.
• Incidence of Adverse Events [Up to 12 months]: The incidence and severity of adverse events occurring during study treatment will be assessed based on clinical symptoms, physical examinations, vital signs, laboratory findings, and other clinically relevant safety parameters. Adverse events will be graded according to the toxicity grading criteria specified in the study protocol.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Histologically confirmed acute myeloid leukemia (AML) with relapsed or refractory disease, including:

   * Refractory AML, defined as failure to achieve remission after at least one prior treatment;
   * Relapsed AML, defined as ≥5% blasts in the bone marrow after a previous remission;
   * AML arising from myelodysplastic syndrome (including CMML) or myeloproliferative neoplasms (secondary AML or therapy-related AML \[t-AML\]) is also eligible.
2. Age ≥18 years, regardless of sex, with an expected survival of >3 months.
3. Estimated creatinine clearance ≥50 mL/min.
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × the upper limit of normal (ULN), unless the abnormality is considered attributable to leukemic organ involvement; total bilirubin ≤3.0 × ULN, unless the abnormality is considered attributable to leukemic organ involvement.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Participants must not be pregnant and must agree to use effective contraception during study treatment.
7. Ability to understand the study and willingness to provide written informed consent.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL).
2. Active central nervous system leukemia.
3. Clinically significant cardiovascular disease, including any of the following:

   * Clinically significant QTc prolongation (QTc >450 ms in males or >470 ms in females);
   * Ventricular tachycardia;
   * Second-degree atrioventricular block;
   * Myocardial infarction within 1 year prior to enrollment;
   * Congestive heart failure;
   * Coronary artery disease requiring medical treatment.
4. Active, uncontrolled severe infection.
5. Other non-hematologic malignancies within the previous 2 years.
6. Psychiatric disorders that may interfere with participation in the study.
7. Previous solid organ transplantation. Prior stem cell transplantation (SCT) is permitted; however, patients with graft-versus-host disease (GVHD) or those receiving ongoing immunosuppressive or GVHD-directed therapy are not eligible.
8. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.

• Bing Xu, Principal investigator, The First Affiliated Hospital of Xiamen University