Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated AML

Study Overview
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Brief Summary
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In this prospective study, 30 newly untreated elderly patients with acute myeloid leukemia(AML) who were not suitable for standard chemotherapy were enrolled to observe the efficacy and side effects of venetoclax (VEN) combined with azacytidine (AZA) and chemotherapy in newly treated elderly patients with AML. Overall survival (OS), complete remission rate/complete remission with incomplete recovery of blood cell count (CR/ CRi) were used as the primary endpoints, and time to response (TTR), duration of response (DOR), mortality, and recurrence rate were used as secondary endpoints,and the incidence of adverse events were evaluated.

Detailed Description
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Induction therapy: venetoclax d1 100mg, d2 200mg, d3-28 400mg, po; azacytidine 75mg/m2, d1-7, sc. Consolidation therapy: Regimen A or B was chosen according to the wishes of the patients. In addition, venetoclax was used for 14 days for positive minimal residual disease(MRD) and 7 days for MRD negative. regimen A: the first two cycles: venetoclax 400mg, d1-7/14, po; cladribine 5mg/m2, d1-3, ivgtt; cytarabine 10mg/m2, q12h, d1-10, sc; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; regimen B: the first two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 100mg/m2, d1-5/7, ivgtt; idarubicin 8mg/m2, d1-2/3, ivgtt; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; If the patient's ECOG performance status ≥2, the reduction of regimen IA(cytarabine+idarubicin)was 5+2. Maintenance therapy: azacytidine 75mg/m2, d1-7, sc.

Official Title
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Clinical Study of Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Azacitidine
* Drug: Cladribine
* Drug: Cytarabine
* Drug: Idarubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The elderly patients(≥ 60) with AML diagnosed according to WHO criteria; Participants are ineligible for induction regimen; The Eastern Cooperative Oncology Group (ECOG) performance status is 0-3; The patients and their families agree and sign the informed consent form. Exclusion Criteria: Previous treatment for AML (including hypomethylating agents and other chemotherapy drugs); Infiltration of the central nervous system; Drugs use history affecting CYP3A within 7 days before enrollment; participants considered by the investigator to be unsuitable for inclusion.

Ages Eligible for Study
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Minimum Age: 60 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: Venetoclax group<br>Induction therapy: venetoclax d1 100mg, d2 200mg, d3-28 400mg, po; azacytidine 75mg/m2, d1-7, sc. Consolidation therapy: Regimen A or B was chosen according to the wishes of the patients. In addition, venetoclax was used for 14 days for positive minimal residual disease(MRD) and 7 days for MRD negative. regimen A: the first two cycles: venetoclax 400mg, d1-7/14, po; cladribine 5mg/m2, d1-3, ivgtt; cytarabine 10mg/m2, q12h, d1-10, sc; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; regimen B: the first two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 100mg/m2, d1-5/7, ivgtt; idarubicin 8mg/m2, d1-2/3, ivgtt; the last two cycles: venetoclax 400mg, d1-7/14, po; cytarabine 0.5-1.0g/m2, d1-3, ivgtt; If the patient's ECOG performance status ≥2,the reduction of regimen IA(cytarabine+idarubicin)was 5+2. Maintenance therapy: azacytidine 75mg/m2, d1-7, sc. | Drug: Venetoclax<br>* given po.<br>* Other names: ABT-199;Drug: Azacitidine<br>* given sc.<br>* Other names: 5-Azacytidine;Drug: Cladribine<br>* given ivgtt.<br>* Other names: 2-CdA;Drug: Cytarabine<br>* given sc or ivgtt.<br>* Other names: Ara-c;Drug: Idarubicin<br>* given ivgtt.<br>* Other names: Idamycin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival will be defined as the number of days from the date of first dose to the date of death. | up to 16 months. | 
| CR/CRi | To assess the percentage of patients achieving CR/CRi according to the International Working Group criteria for AML. | up to 16 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | To assess the percentage of patients achieving CR/CRi or partial remission (PR) according to the International Working Group criteria for AML. | up to 16 months. | 
| Duration of response | Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease. | up to 16 months. | 
| Mortality | The proportion of patients from enrollment to death was recorded. | up to 16 months. | 
| Recurrence rate | Record the proportion of patients with recurrence in the study. | up to 16 months. | 
| Adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. | Adverse events were assessed weekly during the first and second cycles, and every two cycles thereafter (each cycle is 28 days), up to 16 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy, Acute Myeloid Leukemia, Bcl-2 Inhibitors, Azacytidine