Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of venetoclax combined with CACAG regimen in the treatment of newly diagnosed acute myeloid leukemia.

Detailed Description
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Despite the availability of hematopoietic stem cell transplantation and the emergence of many new therapeutic drugs, the prognosis of newly diagnosed acute myeloid leukemia is still poor. In order to improve the outcome of patients with de novo AML, participants developed a venetoclax combined with CACAG regimen in the treatment of de novo AML. In this study, participants intent to evaluate the efficacy and safety of venetoclax combined with CACAG regimen in the treatment of newly diagnosed AML.

Official Title
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Single Arm,Open Label,Phase I Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: azacytidine;cytarabine;aclamycin;Chidamide;venetoclax;granulocyte


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are able to understand and willing to sign the informed consent form (ICF). All patients should aged 14 to75 years,no gender limitation. Patients who are newly diagnosed with AML. 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 active infection 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.)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Experimental: Venetoclax combined CACAG regimen for newly diagnosed AML. All recipients in this arm received azacytidine, cytarabine.aclamycin, chidamide,venetoclax and granulocyte colony-stimulating factor.Azacytidine was uesd as 75 mg/m2/day from day-1 to day-7.Cytarabine was uesd as 75 mg/m2 bid from day-1 to day-5. Aclamycin was uesd as 10 mg/m2/day on day1,3,5). Chidamide was uesd as 30 mg/day on days 0,3. Venetoclax was uesd as 100 mg on day 1, 200 mg on day 2, 400mg from day-3 to day-14.Granulocyte colony-stimulating factor was uesd as 5ug/kg/day from day 0 until agranulocytosis recovery. | Drug: azacytidine;cytarabine;aclamycin;Chidamide;venetoclax;granulocyte<br>* azacytidine (75 mg/m2/day, days 1 to 7). cytarabine (75 mg/m2 bid, days 1 to 5). aclamycin (10 mg/m2/day, day1,3,5). Chidamide (30 mg/day , days 0,3). venetoclax (100 mg day 1, 200 mg day 2, 400mg days 3 to 14 ). granulocyte colony-stimulating factor (5ug/kg/day, day 0 until agranulocytosis recovery)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | 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). | 2 months after study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission (CR) Rate | 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 months after study treatment | 
| CR with Incomplete Blood Count Recovery Rate | All CR criteria except for residual neutropenia (<1.0 x 109/L (1000/µL)) or thrombocytopenia (<100 x 109/L (100,000/µL) | 2 months after study treatment | 
| Partial Remission (PR) Rate: | All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pre-treatment bone marrow blast percentage by at least 50 percent. | 2 months after study treatment | 
| Rate of Minimal Residual Disease (MRD)-Negative Response: | Percentage of participants who achieved MRD-negative response, defined as < 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry or < 0.01% as assessed by PCR of a bone marrow aspirate. | after two courses of chemotherapy (each course is 28 days) | 
| Progression Free Survival (PFS) | PFS was defined as time from the date joining the clinical study to the date of disease progression (PD) or date of death due to any cause, whichever occurred first. | 180 days after study treatment | 
| Overall Survival (OS) | Defined as the time from joining the clinical study to death due to any cause. | 180 days after study treatment | 
| Rate of Participants With Adverse Events | Percentage of Participants with 3 or 4 grade Adverse Events reported through 28 days post last study medication administration. | Through 28 days post last study medication administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venetoclax, CACAG, AML