Clinical trial NCT03620955: Risk-stratified Therapy Based on Molecular Cytogenetic Aberration and Treatment Response in AML
Official title: Risk-stratified Therapy Based on Molecular and Cytogenetic Aberration and Treatment Response in Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Risk-directed Therapy
Cytogenetic Abnormality
Molecular Abnormality
MRD
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Guangzhou First People's Hospital
name: Wuhan General Hospital of Guangzhou Military Command
name: Shenzhen Hospital of Southern Medical University
name: Peking University Shenzhen Hospital
name: Shenzhen Second People's Hospital
name: Zhongshan People's Hospital, Guangdong, China
name: First Affiliated Hospital of Guangxi Medical University
name: Xiangya Hospital of Central South University
name: The Third Xiangya Hospital of Central South University
name: First Affiliated Hospital of Gannan Medical University
name: Peking University People's Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: The First Affiliated Hospital of Zhengzhou University
name: Chenzhou NO. 1 people's Hospital
First posted: 2018-08-08
Enrollment: 1000
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All newly diagnosed AML exclusively of APL with age range from 14 to 60-year old.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: relapse rate
timeFrame: 2 year
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 2 year
measure: disease-free survival (DFS)
timeFrame: 2 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu
role: PRINCIPAL_INVESTIGATOR
References: