Single Arm Study of Azacitidine and Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients

Study Overview
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Brief Summary
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The goal of this clinical research study is to evaluate the safety and efficacy of Azacytidine in combination with Venetoclax in patients with newly diagnosed fit acute myeloid leukemia.

Detailed Description
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The Study Drug: Azacitidine is a DNA Demethylated drug, which is approvd for treatment of elderly AML patients Venetoclax targets the anti-apoptotic protein Bcl-2 and the process of oxidative phosphorylation to induce apoptosis of leukemia cells and exhibits anti-tumor activity. Study Group: single arm: AZA plus Venetoclax Study Drug Administration: Each course is 28 days long. Venetoclax is taken once daily by oral. The doses of Venetoclax is 100 mg on Day 1, 200 mg on Day 2, reaching a target dose of 400 mg on Day 3 and continuing through Day 28. If concomitantly receiving azoles, the dose of Venetoclax will be adjusted according to the instructions. Azacitidine is taken 75mg/m2 on Days 1-7. Subjects would received 1-2 cycles induction therapy. Once get remission, subjects would received the same indution therapy of middle to high dose of cytarabine based chemotherapy at the discretion of the physician for consolidation. Allo-HSCT is suggested for subjects with the moderate to adverse ELN2017 risk. Study Visit: After treatment, relapse and survival will be followed monthly by telephone, on-site visits, and/or study medical records for up to two years (calculated from the first day of induction therapy); Thereafter follow-up every 3 months for one year.

Official Title
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To Evaluate Safety and Efficacy of Azacitidine Combination With Venetoclax for Treatment of Newly Diagnosed Fit Acute Myeloid Leukemia Patients：A Multicenter, Single-arm Study

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Azacitidine
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Age 45 to 65 years old,both male and female 2.Be able to understand and sign informed consent 3.Untreated AML patients (non-APL) diagnosed according to the 2016 World Health Organization (WHO) classification and diagnostic criteria for acute myeloid leukemia 4.Patients with an ECOG performance status 0,1,2 or 3 5.Expected survival time≥3 months 6.Laboratory indicators meet the following standards: Bilrubin, ALT and AST were all less than 3 times the upper limit of normal within 7 days before the first day of treatment Serum creatinine clearance rate is greater than 30ml/min Exclusion Criteria: 1.patients participating in other interventional or observational clinical studies currently 2.Patients has a history of myeloproliferative neoplasm [MPN] 3.Patients with acute promyelocytic leukemia 4.Active CNS involvement in patients with acute myeloid leukemia 5.Patients with active hepatitis B or C, HIV infection before enrollment 6.Cardiovascular status of patients evaluate by NYHA classification method > 2 7.Patients have chronic respiratory disease requiring continuous oxygen treatment, or any sitiuation investigator believes will adversely affect this study (including renal, neurological, psychiatric, endocrine, metabolic, immune, hepatic, cardiovascular disease and known history of allergy to any study drug) 8.Patients suffering from malabsorption syndrome or other diseases that prevent the enteral route of administration 9.patients present with an uncontrolled systemic infection (viral, bacterial, or fungal) 10.Patients with a history of other malignancies within 2 years before enrollment, except for the following cases: Adequately treated carcinoma in situ of the cervix or carcinoma of the breast Basal cell carcinoma or localized squamous cell carcinoma of skin

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 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: Azacitidine combined with Venetoclax<br>Each course is 28 days long. Subjects with newly diagnosed AML receive Venetoclax once daily by oral. The doses of Venetoclax is 100 mg on Day 1, 200 mg on Day 2, reaching a target dose of 400 mg on Day 3 and continuing through Day 28. If concomitantly receiving azoles, the dose of Venetoclax will be adjusted according to the instructions. At the same time patients will receive Azacitidine 75mg/m2 subcutaneous on Days 1-7.The induction therapy includes 1-2 cycle until subjects get remission. Once complete remission, subjects will receive consolidation. Azacitidine combined with Venetoclax or middle to high dose of arabinoside based chemotherapy would be given at the discretion of the physician. | Drug: Azacitidine<br>* Subjects will receive Azacitidine 75 mg/m2 on days 1-7.Each course is 28 days long.<br>* Other names: 5-aza;Drug: Venetoclax<br>* Subjects would receive Venetoclax once daily by oral. The doses of Venetoclax is 100 mg on Day 1, 200 mg on Day 2, reaching a target dose of 400 mg on Day 3 and continuing through Day 28. Each course is 28 days long.<br>* Other names: Venclyxto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve the CR + CRi + Partial Remission (PR) as evaluated by the investigator. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal residual disease (MRD) negative response rate | The number of subjects who obtained MRD negative as a percentage of all evaluable subjects. | Up to 36 months | 
| Duration of Remission (DOR) | From the first achievement of PR, CR, or CRi to time of disease progression | Up to 36 months | 
| Allogeneic Hematopoietic Stem Cell Transplantation Rate | Proportion of subsequent allogeneic hematopoietic stem cell transplantation in intermediate-risk and adverse-risk patients | Up to 36 months | 
| Overall Survival (OS) | From start of protocol treatment to time of death due to any cause, or until last follow-up | Up to 36 months | 
| Event-Free Survival (EFS) | From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier; or until last follow-up | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, Newly Diagnosed AML, Azacitidine, Venetoclax, Induction Therapy