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

Sponsor

Ge Zheng (Other)

Overall Status

Recruiting

CT.gov ID

NCT04490707

Collaborator

(none)

Enrollment

Location

Arms

27.9

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia in Remission	Drug: Azacitidine Drug: Lenalidomide	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azacitidine plus Lenalidomide (AZA+LEN) 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 Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine Other Names: AZA Drug: Lenalidomide Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Lenalidomide Other Names: LEN
Experimental: Azacitidine(AZA) 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 Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine Other Names: AZA
No Intervention: Observation Arm 3(Observation): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter observation.

Arm

Intervention/Treatment

Experimental: Azacitidine plus Lenalidomide (AZA+LEN)

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

Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine

Other Names:

AZA

Drug: Lenalidomide

Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Lenalidomide

Other Names:

LEN

Experimental: Azacitidine(AZA)

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

Elderly or unfit for intensive therapy patients with acute myeloid leukemia who had entered CR receive maintenance therapy contained Azacitidine

Other Names:

AZA

No Intervention: Observation

Arm 3(Observation): Elderly or unfit for intensive therapy AML patients who had achieved CR after remission-induction and consolidation chemotherapy enter observation.

Outcome Measures

Primary Outcome Measures

DFS [From date of randomization or complete remission until the date of first documented disease progression from any cause,assessed up to 100weeks]
DFS in months, in present of disease free survival period of all participants
OS [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]
OS in months, in present of over all survival period of all participants

Secondary Outcome Measures

Adverse events rates [From date of randomization or initial treatment until the end date of the study, assessed up to 100 weeks]
Adverse events rates in percentage

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.