Study of Azacytidine Combined With Lenalidomide As Maintenance Therapy Based on MRD Monitoring in AML

Study Overview
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Brief Summary
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Great progress has been witnessed on the treatment of acute myeloid leukemia (AML) in recent years. However, elderly patients ineligible for receiving high dose chemotherapy and allo-HSCT, have high relapse rate and treatment-related complications. Azacitidine (AZA), a listed hypomethylating agent in China in 2018, is the only approved demethylating drug in the treatment of AML, following the NCCN guidelines. In addition, lenalidomide(LEN) has been shown to rapidly enhance cytotoxic T- and natural killer (NK)-cell function and reduce relapse post-chemotherapy in patients with MM, also has substantial activity as a single agent in elderly patients with AML. Measurable residual disease (MRD) has been proven to be highly prognostic in quite a number clinical studies. This study is aimed to validate the efficacy and safety advantages of the maintenance therapy that contain AZA and LEN in elderly or unfit for intensive therapy patients with AML based on MRD monitoring.

Detailed Description
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In this study, elderly or unfit for intensive therapy AML patients who had achieved complete remission(CR) after remission-induction and consolidation chemotherapy were assigned to 3 Arms: (1) Maintenance therapy with AZA combined with LEN（AZA+LEN）: AZA 50mg/m² per day for days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or progression; (2) Maintenance therapy with AZA only: AZA 50mg/m² per day for days 1-5, every 28 days for up to 12 cycles or progression; (3) Observation or with supporting therapy. MRD will be assessed by flow cytometry and molecular techniques. The efficacy and safety of the 3 Arms will be evaluated in this study.

Official Title
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Clinical Study of Azacytidine Combined With Lenalidomide As Maintenance Therapy Based on MRD Monitoring In Elderly or Unfit Patients With Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia in Remission

Intervention / Treatment
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* Drug: Azacitidine
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with acute myeloid leukemia.Meet the criteria of the 2016 WHO classification system(APL were excluded), based on morphology, immunology, cytogenetics and molecular biology (MICM) diagnosis. Complete remission was evaluated according to 2020 NCCN guidelines after induction treatment. Patients with age≥ 60 years; or age<60 years unfit for intensive chemotherapy. Volunteered to sign the informed consent. Exclusion Criteria: Mental disorders or other conditions that cannot meet the requirements of research, treatment and monitoring. Allergic to Azacytidine, Lenalidomide , or other drugs of this study Age over 80 years. Any other conditions considered by the study investigators that are not suitable for participating in this clinical trial.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azacitidine plus Lenalidomide (AZA+LEN)<br>Arm 1(AZA+LEN): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA combined with LEN: AZA 50mg/m² per day for days 1-5 and LEN 10mg per day orally for days 6-26 , every 28 days for up to 12 cycles or progression. AZA -Azacitidine, LEN- Lenalidomide | Drug: Azacitidine<br>* Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine<br>* Other names: AZA;Drug: Lenalidomide<br>* Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Lenalidomide<br>* Other names: LEN;|
| Experimental: Azacitidine(AZA)<br>Arm 2 (AZA): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter maintenance therapy with AZA 50mg/m² per day for days 1-5, every 28 days for up to 12 cycles or progression. AZA -Azacitidine | Drug: Azacitidine<br>* Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine<br>* Other names: AZA;|
| No Intervention: Observation<br>Arm 3(Observation): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter observation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | DFS in months, in present of disease free survival period of all participants | From date of randomization or complete remission until the date of first documented disease progression from any cause,assessed up to 100weeks | 
| OS | OS in months, in present of over all survival period of all participants | From date of randomization until the date of first documented death from any cause or end of this study, whichever come first,assessed up to 100weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events rates | Adverse events rates in percentage | From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, Azacitidine, Lenalidomide, Maintenance Therapy, MRD