Azacitidine Combined With Venetoclax and ATRA in Newly Diagnosed AML

Study Overview
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Brief Summary
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This is a single arm study to evaluate the safety and efficiency of azacitidine (AZA) combination with venetoclax and ATRA in Patients With Newly diagnosed acute myeloid leukemia. Azacitidine, venetoclax and ATRA, may stop the growth of cancer cells, either by demethylation, by promoting cells differentiation or by killing the cells.

Detailed Description
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This study include newly diagnosed AML patients who will accept the therapy with AZA combined with venetoclax and ATRA: (1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28, every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month till progression;

Official Title
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A Single Arm Study to Evaluate the Safety and Efficiency of Azacitidine (AZA) Combination With Venetoclax and ATRA in Patients With Newly Diagnosed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Azacitidine Combined With Venetoclax and ATRA group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed AML according to the WHO (2016) classification of acute myeloid leukemia. Age ≥ 18years. ECOG score: 0-3. White blood cell count ≤ 25*10^9/L Total bilirubin ≤ 3X the institutional upper limit of normal if attributable to hepatic infiltration by neoplastic disease AST (SGOT) and ALT (SGPT) ≤ 3X the institutional upper limit of normal Creatinine clearance ≥30ml/min Exclusion Criteria: Pregnancy or lactation. Acute promylocytic leukemia or chronic myeloid leukemia in blast crisis. Another malignant disease. Uncontrolled active infection. Left ventricular ejection fraction < 0.3 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. Active hepatitis B or hepatitis C infection. HIV infection. Other commodities that the investigators considered not suitable for the enrollment.

Ages Eligible for Study
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Minimum Age: 18 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: AVA（Azacitidine Combined With Venetoclax and ATRA）group<br>(1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28,every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month untill progression; | Drug: Azacitidine Combined With Venetoclax and ATRA group<br>* AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28,every 28 days for up to 2 cycles as the inductive therapy.ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles for consolidate therapy.ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month for Maintenance therapy<br>* Other names: AVA group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of the bone marrow complete response | Rate of the bone marrow complete response after 1 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 1 cycle of inductive therapy | after completion of one induction courses (1st Induction Course is 28 days) and before starting of the 2nd cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of the bone marrow complete response after 2 cycle of inductive therapy | Rate of the bone marrow complete response after 2 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 2 cycle of inductive therapy | after completion of two induction courses (1st Induction Course is 28 days) and before starting of the 1st Consolidation cycle | 
| Minimal Residual Disease (MRD) response | MRD response in bone marrow at the end of 2nd cycle | after completion of two induction courses (one Course is 28 days) and before starting of the 1st Consolidation cycle | 
| Overall Survival (OS) | time from randomization to death from any cause | 2 years | 
| Event Free Survival（EFS） | time from randomization to the relapse ,death or drug is unacceptably toxic | 2 years | 
| Number of adverse events | adverse events are evaluated with CTCAE V5.0. | 2 years | 

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