Risk-stratified Therapy Based on Molecular Cytogenetic Aberration and Treatment Response in AML

• Conditions: Risk-directed Therapy; Molecular Abnormality; Cytogenetic Abnormality; MRD
• Interventions: Other: Justified risk stratification based on MRD after three course chemo therapy

• Registration Number: NCT03620955
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

Risk-stratified therapy based on molecular and cytogenetic for acute myeloid leukemia (AML) is well accepted and benefits patients' survival. However, neither every patient with low risk factors obtains better survival, nor all high risk patients experience worse outcome. Lots of data have shown that the early treatment response presenting as minimal residual disease (MRD) has an important role in prognostic prediction. In this study, we perform risk stratification based on not only Cytogenetic and Molecular characteristic, but also MRD after three courses of chemo therapy in AML cohort. Patients with MRD positive would be moved to a higher risk class. And then the risk-stratified therapy should be considered according to the new risk stratification.

Detailed Description

Risk-stratified therapy based on cytogenetic and molecular characteristic for acute myeloid leukemia (AML) is well accepted and benefits patients' survival. However, neither every patient with low risk factors obtains better survival, nor all high risk patients experience worse outcome. Lots of data have shown the important role of early treatment response presenting as minimal residual disease (MRD) in prognostic prediction. In this study, we perform risk stratification based on not only cytogenetic and molecular characteristic, but also MRD levels after three courses of chemo therapy. We stratified all patients into different risk groups according to the NCCN guild based on cytogenetic and molecular. Then we treat all patients with anthracycline combined with cytarabine regimens for two courses (First cycle: IDA 12mg/m2 or DNR 60mg/m2, d1-3, Ara-C 100mg/m2 d1-7; Second cycle: IDA 10mg/m2 or DNR 45mg/m2, d1-3, Ara-C 2g/m2 q12h, d1-3) . The patients without obtaining complete remission (CR) will go on one cycle of salvage therapy and then be bridged to allogeneic (allo-) hemopoietic stem cell transplantation (HSCT). Those acquiring CR will be given one course of high dose cytarabine (HDAC) as consolidation treatment and then be detested MRD with flow cytometry after that. The patients with MRD positive would be moved to a higher risk class.The stratified therapy should be considered according to the new risk stratification.The patients with MRD negative in low risk group are given HDAC (Ara-C 2g/m2 q12h, d1-3) for 3 cycles. If MRD is continuously negative in this cohort, chemotherapy will be stopped and MRD will be continuously monitored to the third year after the diagnosis. The patients with MRD negative in medium risk group are suggested to receive allo-HSCT if a HLA-matched sibling donor is available, or autologous (auto-) HSCT after receiving HDAC regimen for one more cycle if no HLA-matched sibling donors are available. The patients with MRD positive in low or medium-risk group or the cases in high-risk group are going to be bridged into allo-HSCT if a donor is available including haploid donors. The aim of this study is to evaluate whether the new stratification system benefits AML patients with better OS and DFS.

Study Timeline

• Study First Submitted: 2018-08-05
• Study First Submitted QC: 2018-08-05
• Study First Posted: 2018-08-08
• Study Start: 2018-08-10
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-31
• Last Update Posted: 2019-11-04
• Primary Completion: 2020-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

All newly diagnosed AML exclusively of APL with age range from 14 to 60-year old

Exclusion Criteria

Any abnormality in a vital sign (e.g., organ function failure, serious infection ) Patients with any conditions not suitable for the trial (investigators' decision)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Risk stratification	Justified risk stratification based on MRD after three course chemo therapy	Risk stratification based on cytogenetic and molecular and MRD level after three courses of chemo therapy.

Primary Outcome Measures

Name	Time	Method
relapse rate	2 year

Secondary Outcome Measures

Name	Time	Method
disease-free survival (DFS)	2 year
overall survival (OS)	2 year

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China