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

Venetoclax Combined With CACAG Regimen Versus "3+7" Regimen in the Treatment of Acute Monocytic Leukemia: A Prospective, Randomized, Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Monocytic Leukemia
• Intervention / Treatment: Drug: CACAG+VEN; Drug: 3+7

Detailed Description

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 Participants who do not achieve at least a partial response after the first cycle may be withdrawn from the study to receive alternative treatment as recommended by clinical guidelines.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.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daihong Liu, Doctor; Phone Number: +8613681171597; Email: daihongrm@163.com
• Study Contact Backup: Name: Liping Dou, Doctor; Phone Number: +8613681207138; Email: lipingruirui@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Daihong Liu, Doctor; Phone Number: +8613681171597; Email: daihongrm@163.com
    • Contact: Liping Dou, Doctor; Phone Number: +8613681207138; Email: lipingruirui@163.com
  • Beijing, China
    • Recruiting
    • Air Force Medical Center, PLA
    • Contact: Liping Dou, Doctor; Phone Number: +8613681207138; Email: lipingruirui@163.com
  • Beijing, China
    • Recruiting
    • PLA Strategic Support Force's Characteristic Medical Center
    • Contact: Liping Dou, Doctor; Phone Number: +8613681207138; Email: lipingruirui@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax Combined with CACAG Regimen; Participants assigned to Venetoclax Combined with CACAG Regimen will receive a combination regimen consisting of venetoclax plus the CACAG. The CACAG regimen includes azacitidine administered at a dose of 75 mg/m² subcutaneously on days 1-7; cytarabine given at a dose of 75-100 mg/m² q12h intravenously on days 1-5; aclarubicin administered at a dose of 20 mg intravenously on days 1, 3, and 5; and chidamide given orally at a dose of 30 mg twice a week for two weeks. 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. Granulocyte colony-stimulating factor (G-CSF) is given subcutaneously at 300 μg per day until neutrophil recovery. Each treatment cycle lasts 4-5 weeks, with a total of 2 cycles.	Drug: CACAG+VEN; Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor; Azacytidine (75 mg/m2/day, days 1 to 7).; Cytarabine (75-100 mg/m2 every 12 hrs, days 1 to 5).; Aclacinomycin (20 mg/day, days 1,3,5).; Chidamide (30 mg/day , days 1,4,8,11).; 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.
Active Comparator: Standard "3+7" Regimen; Participants assigned toStandard "3+7" Regimen will receive the standard "3+7" induction regimen. Daunorubicin is administered intravenously at a dose of 60 mg/m² on days 1-3. Cytarabine is given intravenously at a dose of 75-100 mg/m² twice daily on days 1-7. Each treatment cycle lasts 4-5 weeks, with a total of 2 cycles. Participants who do not achieve at least a partial response after the first cycle will be withdrawn from the study and receive alternative treatment according to clinical guidelines.	Drug: 3+7; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Remission Rate	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).	At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate after Cycle 1	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.	At the end of Cycle 1 (each cycle is 28 days)
Complete Remission with Incomplete Count Recovery Rate after Cycle 1	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).	At the end of Cycle 1 (each cycle is 28 days)
Overall Response Rate after Cycle 1	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).	At the end of Cycle 1 (each cycle is 28 days)
Partial Remission Rate after Cycle 1	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.	At the end of Cycle 1 (each cycle is 28 days)
Minimal Residual Disease Negative Rate after Cycle 1	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.	At the end of Cycle 1 (each cycle is 28 days)
Composite Complete Remission Rate after Cycle 1	Proportion of participants achieving composite complete remission (CRc = CR + CRi) after two cycles of treatment.	At the end of Cycle 1 (each cycle is 28 days)
Complete Remission Rate after Cycle 2	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.	At the end of Cycle 2 (each cycle is 28 days)
Complete Remission with Incomplete Count Recovery Rate after Cycle 2	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).	At the end of Cycle 2 (each cycle is 28 days)
Partial Remission Rate after Cycle 2	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.	At the end of Cycle 2 (each cycle is 28 days)
Minimal Residual Disease Negative Rate after Cycle 2	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.	At the end of Cycle 2 (each cycle is 28 days)
Progression-Free Survival	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.	Up to 12 months after enrollment
Overall Survival	The time from enrollment to death from any cause. For surviving participants, data will be censored at the date of last follow-up.	Up to 12 months after enrollment
Relapse Rate	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.	Up to 12 months after enrollment
Duration of Remission	The time from the first documented remission (CR or CRi) to disease relapse or death from any cause, whichever occurs first.	Up to 12 months after enrollment
Adverse reactions in hematology	Record of adverse events in hematological system during and after treatment	At the end of Cycle 2 (each cycle is 28 days)
Nonhematological adverse reactions	Record of adverse events in other organs or systmes during and after treatment	At the end of Cycle 2 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: Air Force Medical Center of PLA; PLA Strategic Support Force's Characteristic Medical Center
• Investigators: Principal Investigator: Liping Dou, Doctor, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Acute Monocytic Leukemia; Venetoclax+CACAG
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Hemic and Lymphatic Diseases; Leukemia, Monocytic, Acute
• Other Study ID Numbers: 2025-761

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No