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

MRD Clinical Trial

Official title:

Risk-stratified Therapy Based on Molecular and Cytogenetic Aberration and Treatment Response in Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03620955
• Other study ID #: Risk stratification in AML
• Status: Recruiting
• Start date: August 10, 2018
• Est. completion date: December 2021

Study information

• Verified date: October 2019
• Source: Nanfang Hospital of Southern Medical University
• Contact: Qifa Liu
• Email: liuqifa628[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chromosome Aberrations
• Chromosome Disorders
• Congenital Abnormalities
• Cytogenetic Abnormality
• Molecular Abnormality
• MRD
• Risk-directed Therapy

Intervention

Other:
• Justified risk stratification based on MRD after three course chemo therapy
All patients are routinely divided into different risk groups according to the NCCN guild based on cytogenetic and molecular abnormality. Then all patients are treated with anthracycline combined with cytarabine regimens for two courses . The patients without obtaining CR will go on one cycle of salvage therapy and then be bridged to allo-HSCT. Those acquiring CR will be given one more course of 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.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (17)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

Chenzhou NO. 1 people's Hospital, First Affiliated Hospital of Gannan Medical University, First Affiliated Hospital of Guangxi Medical University, Guangzhou First People's Hospital, Peking University People's Hospital, Peking University Shenzhen Hospital, Second Affiliated Hospital, Sun Yat-Sen University, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shenzhen Hospital of Southern Medical University, Shenzhen Second People's Hospital, The First Affiliated Hospital of Zhengzhou University, The Third Xiangya Hospital of Central South University, Third Affiliated Hospital, Sun Yat-Sen University, Wuhan General Hospital of Guangzhou Military Command, Xiangya Hospital of Central South University, Zhongshan People's Hospital, Guangdong, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	relapse rate		2 year
Secondary	overall survival (OS)		2 year
Secondary	disease-free survival (DFS)		2 year