Venetoclax Combined With CACAG Regimen Versus "3+7" Regimen in the Treatment of Acute Monocytic Leukemia

This study is a multicenter, randomized, prospective Phase II clinical trial designed to compare the effectiveness of two treatment approaches for patients with acute monocytic leukemia.

A total of 204 participants, aged 14 to 60 years, will be enrolled across multiple study sites in China. Participants will be randomly assigned to one of two treatment groups:

Group 1: Venetoclax combined with the CACAG (cytarabine, azacitidine, chidamide, aclarubicin and granulocyte colony-stimulating factor) regimen This group will receive a combination of azacitidine, cytarabine, aclarubicin, chidamide, and venetoclax, along with granulocyte colony-stimulating factor (G-CSF) support.

Group 2: The standard "3+7" regimen This group will receive standard induction chemotherapy with daunorubicin and cytarabine.

The total study treatment period is about 8-10 weeks, consisting of two treatment cycles. Participants who do not achieve at least a partial response after the first cycle may be withdrawn from the study to receive alternative treatment as recommended by clinical guidelines.

The main goal of the study is to evaluate and compare the effectiveness of these two regimens in treating acute monocytic leukemia. Outcomes will include treatment response, safety, and overall patient outcomes during the study period.

• CACAG+VEN (Drug): Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor 1. Azacytidine (75 mg/m2/day, days 1 to 7). 2. Cytarabine (75-100 mg/m2 every 12 hrs, days 1 to 5). 3. Aclacinomycin (20 mg/day, days 1,3,5). 4. Chidamide (30 mg/day , days 1,4,8,11). 5. Venetoclax is administered orally with a dose ramp-up schedule: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3 through 14. If an azole antifungal agent is co-administered, the dose of venetoclax is reduced to 100 mg daily. 6.Granulocyte colony-stimulating factor (G-CSF) is given subcutaneously at 300 μg per day until neutrophil recovery.
• 3+7 (Drug): IA regimen: 1. Idarubicin (8-10 mg/m2) for 3 days. 2.Cytarabine (75-100mg/m2, every 12 hrs) for 7 days. DA regimen: 1.Daunorubicin(60 mg/m2) for 3 days. 2.Cytarabine (75-100mg/m2, every 12 hrs) for 7 days. MA regimen: 1.Mitoxantrone (12 mg/m2) for 3 days. 2.Cytarabine (75-100mg/m2, every 12 hrs) for 7 days.

Primary outcomes

• Composite Complete Remission Rate [At the end of Cycle 2 (each cycle is 28 days)]: Proportion of participants achieving composite complete remission (CRc = CR + CRi) after one cycle of treatment. CR is defined as no clinical leukemic symptoms, hemoglobin ≥100 g/L (male) or ≥90 g/L (female/children), ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, no blasts in peripheral blood, and bone marrow blasts ≤5% with normal erythroid and megakaryocytic lineages. CRi meets all CR criteria except residual neutropenia (ANC <1.0×10⁹/L) or thrombocytopenia (platelets <100×10⁹/L).

Secondary outcomes

• Complete Remission Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving complete remission (CR) after one cycle of treatment. CR is defined as absence of clinical symptoms and signs of leukemic infiltration; hemoglobin ≥100 g/L (male) or ≥90 g/L (female and children), absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, no blasts in peripheral blood differential, and bone marrow blasts (type I + II) ≤5% with normal erythroid and megakaryocytic lineages.
• Complete Remission with Incomplete Count Recovery Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving complete remission with incomplete count recovery (CRi) after one cycle of treatment. CRi is defined as meeting all CR criteria except for residual neutropenia (absolute neutrophil count <1.0×10⁹/L) or thrombocytopenia (platelet count <100×10⁹/L).
• Overall Response Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving overall response after one cycle of treatment. Overall response is defined as the sum of complete remission (CR), complete remission with incomplete count recovery (CRi), and partial remission (PR).
• Partial Remission Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving partial remission (PR) after one cycle of treatment. PR is defined as a reduction of bone marrow blasts by more than 50%, with a final blast percentage between 5% and 25%, and recovery of peripheral blood counts to normal.
• Minimal Residual Disease Negative Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving minimal residual disease (MRD) negativity after one cycle of treatment. MRD negativity is defined as the absence of measurable residual disease as assessed by immunologic or molecular methods.
• Composite Complete Remission Rate after Cycle 1 [At the end of Cycle 1 (each cycle is 28 days)]: Proportion of participants achieving composite complete remission (CRc = CR + CRi) after two cycles of treatment.
• Complete Remission Rate after Cycle 2 [At the end of Cycle 2 (each cycle is 28 days)]: Proportion of participants achieving complete remission (CR) after two cycles of treatment. CR is defined as absence of clinical symptoms and signs of leukemic infiltration; hemoglobin ≥100 g/L (male) or ≥90 g/L (female and children), absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, no blasts in peripheral blood differential, and bone marrow blasts (type I + II) ≤5% with normal erythroid and megakaryocytic lineages.
• Complete Remission with Incomplete Count Recovery Rate after Cycle 2 [At the end of Cycle 2 (each cycle is 28 days)]: Proportion of participants achieving complete remission with incomplete count recovery (CRi) after two cycles of treatment. CRi is defined as meeting all CR criteria except for residual neutropenia (absolute neutrophil count <1.0×10⁹/L) or thrombocytopenia (platelet count <100×10⁹/L).
• Partial Remission Rate after Cycle 2 [At the end of Cycle 2 (each cycle is 28 days)]: Proportion of participants achieving partial remission (PR) after two cycles of treatment. PR is defined as a reduction of bone marrow blasts by more than 50%, with a final blast percentage between 5% and 25%, and recovery of peripheral blood counts to normal.
• Minimal Residual Disease Negative Rate after Cycle 2 [At the end of Cycle 2 (each cycle is 28 days)]: Proportion of participants achieving minimal residual disease (MRD) negativity after two cycles of treatment. MRD negativity is defined as the absence of measurable residual disease as assessed by immunologic or molecular methods.
• Progression-Free Survival [Up to 12 months after enrollment]: The time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first. Disease progression is defined according to standard criteria for acute monocytic leukemia.
• Overall Survival [Up to 12 months after enrollment]: The time from enrollment to death from any cause. For surviving participants, data will be censored at the date of last follow-up.
• Relapse Rate [Up to 12 months after enrollment]: The proportion of participants who achieve remission (CR or CRi) and subsequently experience disease relapse during the follow-up period. Relapse is defined according to standard criteria for acute monocytic leukemia.
• Duration of Remission [Up to 12 months after enrollment]: The time from the first documented remission (CR or CRi) to disease relapse or death from any cause, whichever occurs first.
• Adverse reactions in hematology [At the end of Cycle 2 (each cycle is 28 days)]: Record of adverse events in hematological system during and after treatment
• Nonhematological adverse reactions [At the end of Cycle 2 (each cycle is 28 days)]: Record of adverse events in other organs or systmes during and after treatment

Sex: All, ages: 14 Years to 60 Years

Inclusion Criteria:

* Voluntary participation with written informed consent signed by the participant or a legal guardian; willingness to comply with all study procedures.
* Age 14 to 60 years at screening, no gender restriction.
* Diagnosis of acute monocytic leukemia according to the 2016 WHO classification, excluding acute promyelocytic leukemia.
* No history of severe allergic reactions.
* Liver function: ALT and AST ≤ 2.5 × upper limit of normal (ULN); total bilirubin ≤ 2 × ULN.
* Renal function: serum creatinine ≤ 1.5 × ULN
* No uncontrolled infection or severe psychiatric disorder.
* ECOG performance status 0-3; life expectancy ≥ 4 months.

Exclusion Criteria:

* Known hypersensitivity or contraindication to any study drug.
* Pregnancy or lactation.
* Active infection.
* Long-term smoking or alcohol abuse that may interfere with study outcome evaluation.
* Psychiatric illness or other condition that prevents informed consent or compliance with study procedures.
* Major organ surgery within 6 weeks prior to enrollment.
* Abnormal liver function: total bilirubin > 2× ULN, ALT/AST > 2.5 × ULN; abnormal renal function: serum creatinine > 1.5 × ULN.
* Any condition deemed unsuitable for the study by the investigator (e.g., poor compliance, substance abuse).

• Liping Dou, Doctor, Principal investigator, Chinese PLA General Hospital