Safety and Efficacy of Venetoclax in Combination With Azacitidine and HA Regimen in the Treatment of AML in the Elderly

Study Overview
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Brief Summary
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This is a prospective phase II, single-arm clinical study that plans to enroll 45 patients aged 60 years or older with primary AML diagnosed after April 1, 2023.The purpose of this trial is to evaluate the efficacy of Venetoclax in combination with azacitidine and HA regimens in elderly patients aged >60 years with primary acute myeloid leukemia and to provide evidence for optimal selection of clinical treatment regimens.

Detailed Description
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Patients diagnosed with primary AML according to morphology, immunophenotyping and medical history and meeting the exclusion criteria for enrollment: induction therapy with Venetoclax combined with azacitidine and HA regimen, after induction therapy up to CR, CRi, MLFS, according to ELN prognostic stratification and NCCN and Chinese guidelines for the treatment of adult AML (non-acute promyelocytic leukemia), according to patient risk stratification and treatment For patients with allogeneic hematopoietic stem cell transplantation due to various reasons (financial, physical, and other reasons), the patient will be recommended for transplantation. Patients who are not considered for allogeneic HSCT due to various reasons (financial, physical, donor constraints, etc.) will continue to receive two courses of intensive treatment with Venetoclax combined with a medium-dose Ara-c regimen and three courses of reduced-dose chemotherapy for consolidation. Patients completing intensive consolidation therapy enter maintenance treatment with Venetoclax in combination with azacitidine, danazol and thalidomide. Patients who do not achieve CR, CRi and MLFS with 1 course of induction therapy will be re-induced with the original regimen if they achieve PR. Patients who did not achieve PR on the first induction treatment and did not achieve CR, CRi, and MLFS after two induction treatments were dropped from the group and given salvage therapy. Patients with persistent positive MRD or recurrence during treatment were withdrawn from the group and given salvage therapy.

Official Title
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The Second Affiliated Hospital of Kunming Medical University

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Procedure: Venetoclax in Combination With Azacitidine and HA Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with acute myeloid leukemia other than APL who meet the World Health Organization diagnostic criteria (WHO 2016 criteria); those with AML not otherwise classified under the World Health Organization AML classification except for acute myeloproliferative disorder with myelofibrosis and myeloid sarcoma. Age > 60 years, male or female. Have a score of 0-2 on the Eastern Cooperative Oncology Group Physical Status Scale (ECOG-PS). pass the requirements of the following laboratory test indicators (performed within 7 days prior to treatment): 1) Aspartate aminotransferase (ALT), alanine aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN), serum bilirubin ≤ 2 x ULN; serum cardiac enzymes < 2.0 x ULN; serum creatinine ≤ 2.0 x ULN; 2) Cardiac ejection fraction within normal values as determined by cardiac ultrasound (ECHO). Informed consent had to be signed before all specific study procedures were started, and the informed consent was signed by the patient himself/herself or his/her immediate family members; in view of the patient's condition, if the signature of the patient himself/herself was not conducive to the treatment of his/her condition, the informed consent was signed by his/her legal guardian or the patient's immediate family members. Exclusion Criteria: 1、Treated patients (is defined as having received induction chemotherapy in the past, regardless of the efficacy). 2, Concurrent malignant tumors of other organs (those requiring treatment). 3, Patients participating in the trial must use contraception during the trial treatment and within 3 years after completion of treatment. 4, Significantly abnormal liver and kidney function beyond the enrollment criteria. 5. Active heart disease, defined as one or more of the following: History of uncontrolled or symptomatic angina; Myocardial infarction less than 6 months from study entry; A history of arrhythmia requiring medication or clinically significant symptoms; Uncontrolled or symptomatic congestive heart failure (> NYHA class 2); Ejection fraction below the lower limit of the normal range. 6. severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis). 7) Those deemed unsuitable for enrollment by the investigator

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Venetoclax in Combination With Azacitidine and HA Regimen<br>Details for: Venetoclax 200mg d1-10 Azacitidine 100mg/d (or 50-75mg/m2/d), d2-7 Hautriacontin 2mg/m2/d, d3-7 Cytarabine 100mg/m2/d, d3-8 (infusion 24h) | Procedure: Venetoclax in Combination With Azacitidine and HA Regimen<br>* Patients diagnosed with primary AML based on morphology, immunophenotyping, and history and meeting the inclusion exclusion criteria were induced with Venetoclax in combination with Azacitidine and HA regimen. Details for: Venetoclax 200mg d1-10 Azacitidine 100mg/d (or 50-75mg/m2/d), d2-7 Hautriacontin 2mg/m2/d, d3-7 Cytarabine 100mg/m2/d, d3-8 (infusion 24h)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | which evaluates the efficacy of patient induction therapy, including complete remission (CR), complete remission with incomplete blood count recovery (CRi), and morphologic leukemia-free state (MLFS) | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal residual disease (MRD) | MRD percentage | up to 12 months | 
| overall survival (OS) | Overall Survival (OS) is used to evaluate all patients enrolled in a clinical trial, from the date of enrollment until death from any cause or the date of last follow-up for surviving patients. | up to 12 months | 
| relapse-free survival (RFS) | Relapse-Free Survival (RFS) is only used to evaluate patients who achieve complete remission (CR) through reinduction therapy. RFS is defined as the time from achievement of CR until death from any cause, relapse, or the date of last follow-up. | up to 12 months | 
| 30-day mortality rate | The 30-day mortality rate is used to evaluate all patients enrolled in a clinical trial, and is defined as the percentage of patients who die within 30 days of starting chemotherapy. | Within 30 days after starting the medication | 
| adverse drug reactions | Adverse drug reactions during chemotherapy and follow-up | up to 12 months |