AZA + Venetoclax as Maintenance Therapy in Younger Adults With AML in First Remission

Study Overview
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Brief Summary
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This phase III trial is conducted to evaluate if azacitidine in combination with venetoclax as maintenance therapy improves relapse-free survival (RFS) for younger adults with favorable-risk acute myeloid leukemia (AML) who remained in first complete remission (CR1) following intensive consolidation.

Official Title
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Randomized, Multicenter, Phase 3 Study of Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With AML in Remissionin Younger Adults With Favorable-risk AML in First Remission After Conventional Chemotherapy

Conditions
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Acute Myeloid Leukemia (AML) in Remission

Intervention / Treatment
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* Drug: Azacitidine
* Drug: Venetoclax
* Other: Supportive care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of favorable-risk acute myeloid leukemia (AML) according to revised 2017 European LeukemiaNet genetic risk stratiﬁcation and are not immediate candidates for allogeneic stem cell transplant. Aged 18-64 years. Patients who have received remission induction therapy and 3-4 HiDAC or medium-dose cytarabine-based consolidation and are in their first remission. ECOG performance status of < or = 3. Adequate organ function as follows: Serum total bilirubin < or = to 3 X the Upper Limit of Normal (ULN) Aspartate Transaminase and alanine transaminase < or = to 3 x ULN Ccr（Creatinine Clearance Rate) > or ＝60 ml/min Left ventricular ejection fraction > or ＝50% determined by ultrasound. For females of childbearing age, they should have a negative serum or urine pregnancy test within 10 to 14 days of enrolling. For males of childbearing age, they should take effective contraceptive methods throughout the treatment period and up to 30 days after discontinuing treatment. Ability to understand and sign informed consent. Exclusion Criteria: Acute promyeloid leukemia. Patients with active central nervous system (CNS) leukemia. Previously diagnosed with myelodysplastic syndrome (MDS) or myeloproliferative neoplasm(MPN) and progressed to AML. Patients with other progressive malignancies. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled and/or active systemic infection (viral, bacterial or fungal). Patients who have participated in other trials within 30 days before signing the informed consent. Females who are pregnant or lactating or intending to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (azacytidine+venetoclax)<br>Participants will receive azacytidine QD, on Days 1-5 and venetoclax QD, on Days 1-14 of each 28-day cycle for 8 cycles. | Drug: Azacitidine<br>* Given SC<br>* Other names: 5-Azacytidine;Drug: Venetoclax<br>* Given PO<br>* Other names: Venclexta;Other: Supportive care<br>* Patients will receive disease monitoring and supportive care for any complication.<br>|
| Experimental: Comparator ( best supportive care)<br>Participants will receive observation and supportive care during remission. | Other: Supportive care<br>* Patients will receive disease monitoring and supportive care for any complication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free survival (RFS) | RFS is defined as the number of days from CR/CRi to the date of relapse or the date of death from any cause, whichever comes first. | From date of complete remission (CR) or complete remission with incomplete count recovery (CRi), to relapse or death from any cause, up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Minimal Minimal Residual Disease (MRD) Negative Conversion | The MRD conversion rate is defined as the percentage of participants deemed MRD positive (≥ 10^-3) at study initiation who converted to MRD of < 10^-3 in the bone marrow after randomization or initiation of treatment. | Measured From Baseline to approximately 3 years | 
| Complete remission duration (CRd) | CRd is defined as time from CR/CRi until date of confirmed relapse | From date of CR/CRi to approximately 3 years | 
| Overall Survival (OS) | OS is defined as the number of days from the date of study treatment to the date of death. | Time from treatment to death from any cause, up to approximately 3 years | 
| Event free survival (EFS) | EFS is defined as time from the start of study treatment until date of first confirmed relapse, withdrawal from study due to adverse event, or death due to any cause, | Time from treatment to relapse，withdrawal from study due to adverse event and death from any cause, up to approximately 3 years | 
| Incidence of adverse events | The NCI Common Toxicity Criteria (CTCAE 5.0) is used to grade adverse events. | Time from treatment to approximately 3 years |