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

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

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.

Study Overview

• Status: Unknown
• Conditions: MRD; Risk-directed Therapy; Cytogenetic Abnormality; Molecular Abnormality
• Intervention / Treatment: Other: Justified risk stratification based on MRD after three course chemo therapy

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 Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University
      • Contact: Qifa Liu
      • Contact: Guopan Yu; Email: yugpp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Risk stratification; Risk stratification based on cytogenetic and molecular and MRD level after three courses of chemo therapy.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
relapse rate	2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival (OS)	2 year
disease-free survival (DFS)	2 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: August 5, 2018
• First Submitted That Met QC Criteria: August 5, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Congenital Abnormalities; Chromosome Disorders; Chromosome Aberrations
• Other Study ID Numbers: Risk stratification in AML

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No