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NCT Number: NCT06084819

Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with BAT regimen in the treatment of relapsed/refractory acute myeloid leukemia.

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Key information

Conditions

Relapsed/Refractory Acute Myeloid Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

14 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

About this study

Despite advances in therapies for acute myeloid leukemia (AML) in the past decades, some patients still suffer from relapsed/refractory (R/R) disease, resulting in poor outcomes. With a median overall survival (OS) of 4-7 months under classic chemotherapy approaches, it is imperative to explore new treatment options.Accumulating research has demonstrated the importance of epigenetic modification in the pathogenesis of chemoresistance. Recent studies have shown that combining venetoclax with hypomethylating agents (HMAs) such as azacitidine, or low-dose cytarabine (LDAC) improves the response and survival rates in R/R AML patients. To enhance the response rate, we designed a regimen that combines chidamide, azacitidine, cytarabine, aclarubicin, and G-CSF with venetoclax (CACAG+VEN regimen) for the treatment of patients with R/R AML. In this study, we intend to compare the efficacy and safety of venetoclax combined with the CACAG regimen with Best-Available Therapy(BAT) regimen in the treatment of relapsed/refractory acute myeloid leukemia.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients who are able to understand and willing to sign the informed consent form (ICF).
  • All patients should aged 14 to 75 years,no gender limitation.
  • Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria
  • Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal;
  • Renal function: creatinine ≤the upper limit of normal;
  • Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
  • The score of Eastern Cooperative Oncology Group (ECOG) is 0-3,and the predicted survival ≥ 4 months.
  • Patients without severe allergic constitution.

Exclusion criteria

  • Patients with allergy or contraindication to the study drug;
  • Female patients who are pregnant or breast-feeding.
  • Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment;
  • Patients with mental illness or other states unable to comply with the protocol;
  • Less than 6 weeks after surgical operation of important organs.
  • Liver function: ALT and AST>2.5 times the upper limit of normal ,bilirubin>2 times the upper limit of normal;Renal function: creatinine >the upper limit of normal;
  • The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)

Treatment and study plan

Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor

Drug
  • Azacytidine (75mg/m2/day, days 1 to 7).
  • Cytarabine (75-100mg/m2 q12h, days 1 to 5).
  • Aclacinomycin(20mg/day, days 1,3,5).
  • Chidamide(30mg/day , days 1,4,8,11).
  • Venetoclax (100mg on day 1,200mg on day 2,400mg on days 3-14).
  • Granulocyte colony stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)

Other names: CACAG+VEN

Best-Available Therapy(BAT) Regimen

Drug
  • FLAG regimen:Fludarabine(30mg/m2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5)
  • CLAG regimen:Cladribine(5mg/2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5)
  • MAE regimen:Mitox(10mg/m2,days 1 to 5)+VP-16(100mg/m2,days 1 to 5)+Cytarabine (100-150mg/m2,days 1 to 7)
  • DCAG regimen:Decitabine(20mg/m2,days 1 to 5)+Aclacinomycin(20mg/day on days 1,3,5)+Cytarabine (100mg q12h,days 1 to 5)+Granulocyte colony-stimulating factor(300 ug/day,day 0 until agranulocytosi recovery)
  • HAA regimen:HHT(2mg/m2,days 1 to 7)+Aclacinomycin(20mg/day,days 1 to 7) and Cytarabine (100-200 mg/m2, days 1 to 5);
  • HAD regimen:HHT(2mg/m2,days 1 to 7)+Daunorubicin(45mg/m2/day,days 1 to 3)+Cytarabine (100-200 mg/m2,days 1 to 5).

Other names: FLAG/CLAG/MAE/DCAG/HAA/HAD Regimen

Primary outcomes

  1. Overall Response Rate (ORR) after 1 course of treatment

    Time frame: 1 months after the start of study treatment

    Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.

Secondary outcomes

  1. Complete Remission (CR) Rate after 1 course of treatment

    Time frame: 2 months after study treatment

    Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.

  2. Complete Remission (CR) Rate after 2 courses of treatment

    Time frame: After two courses of chemotherapy (each course is 28 days)

    Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.

  3. Overall Response Rate (ORR) after 2 course of treatment

    Time frame: After two courses of chemotherapy (each course is 28 days)

    Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.

  4. Rate of Minimal Residual Disease (MRD)-Negative Response

    Time frame: After two courses of chemotherapy (each course is 28 days)

    Percentage of participants who achieved MRD-negative response, defined as < 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry.

  5. Event-free survival

    Time frame: 180 days after study treatment

    Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.

  6. Overall Survival (OS)

    Time frame: 180 days after study treatment

    Defined as the time from joining the clinical study to death due to any cause.

  7. Treatment-related adverse events

    Time frame: From the first dose of study treatment to 30 days after the discontinuation of treatment

    Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment.

  8. Early death

    Time frame: Within 30 days of the start of the first course of treatment

    Defined as death within 30 days of chemotherapy.

  9. Disease-free survival

    Time frame: 180 days after study treatment

    Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.

Study contacts

Contact information is provided by the study sponsor or research team.

Daihong Liu, doctor

CONTACT

[email protected]

+8613681171597

Liping Dou, doctor

CONTACT

[email protected]

+8613681207138

Sponsors and collaborators

Lead sponsor

Chinese PLA General Hospital

Other

Collaborators

  • 940 Hospital of the People's Liberation Army Joint Logistic Support Force
  • 960th Hospital of Joint Logistics Support Force of People's Liberation Army of China
  • Air Force Military Medical University, China
  • First Hospital of China Medical University
  • People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center
  • The General Hospital of Northern Theater Command
  • The General Hospital of Western Theater Command
  • Yantai Yuhuangding Hospital

Registry information

Official study title

A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Important dates

Study start
2023
Primary completion
2029
Study completion
2030
First posted
Oct 16, 2023
Registry last updated
Apr 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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