Individualized Induction Therapy for Non-elderly Acute Myeloid Leukemia Patients With Adverse Risk Features

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04752527

Collaborator

(none)

Enrollment

Location

Arm

21.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Individualized induction therapy will be applied to the non-elderly acute myeloid leukemia (AML) patients with adverse genetic risk features guided by rapid screening with fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), such as the combination of Venetoclax plus decitabine, and Sorafenib for patients with high (FMS)-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) allelic ratio. This study aims to improve induction therapy for non-elderly AML patients with adverse genetic risk features, reduce treatment-related complications, and improve overall survival.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia, Adult	Drug: venetoclax combined with decitabine	Phase 2

Detailed Description

The non-elderly AML patients who meet the adverse risk group defined as 2017 European LeukemiaNet (ELN) risk stratification, are more likely to be refractory to intensive induction and have low rates of long-term survival. Venetoclax (drug name) plus decitabine or azacitidine showed tolerable safety and favorable overall response rate (ORR )(complete remission (CR)+CR with incomplete hematologic recovery (CRi) rate: 67%) in elderly AML patients. In addition, combination therapy with sorafenib, cytarabine and idarubicin was able to induce a high CR rate in non-elderly AML patients with FLT3 mutations and a 1-year probability of survival of 74%. The fast next-generation sequencing together with FISH can identify the adverse genetic risk features in AML patients within 72 hours. Individualized induction therapy will be applied to the non-elderly AML patients with adverse genetic risk features guided by rapid screening with FISH and NGS, such as the combination of venetoclax plus decitabine, and Sorafenib for patients with high FLT3-ITD allelic ratio. This study aims to improve induction therapy for non-elderly AML patients with adverse genetic risk features, reduce treatment-related complications, and improve overall survival.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Clinical Study of Individualized Induction Therapy for Non-elderly Patients With Acute Myeloid Leukemia and Adverse Risk Features Guided by Rapid Screening With FISH and NGS

Actual Study Start Date :

Feb 20, 2021

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment regime combination of venetoclax plus azacitidine, and Sorafenib for patients with high FLT3-ITD allelic ratio	Drug: venetoclax combined with decitabine combination of venetoclax plus decitabine, and sorafenib for patients with high FLT3-ITD allelic ratio. (On day 1 of cycle 1, decitabine 20 mg/m2 will be given intravenously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 28 day cycle is finished. For patients with high FLT3-ITD allelic ratio, sorafenib was administered at a dose of 400mg orally twice daily, on days 3 through 28. Other Names: combination of venetoclax plus decitabine with or without sorafenib

Arm

Intervention/Treatment

Experimental: Treatment regime

combination of venetoclax plus azacitidine, and Sorafenib for patients with high FLT3-ITD allelic ratio

Drug: venetoclax combined with decitabine

combination of venetoclax plus decitabine, and sorafenib for patients with high FLT3-ITD allelic ratio. (On day 1 of cycle 1, decitabine 20 mg/m2 will be given intravenously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 28 day cycle is finished. For patients with high FLT3-ITD allelic ratio, sorafenib was administered at a dose of 400mg orally twice daily, on days 3 through 28.

Other Names:

combination of venetoclax plus decitabine with or without sorafenib

Outcome Measures

Primary Outcome Measures

CR/CRi/morphologic leukemia free state (MLFS) [Study start date to study end date, or death, whichever comes first, up to 4 years]
Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State（after one cycle or two cycles of induction therapy）

Secondary Outcome Measures

Event Free Survival(EFS) [Study start date to study end date, or death, whichever comes first, up to 4 years]
Event Free Survival
Overall Survival(OS) [Study start date to study end date, or death, whichever comes first, up to 4 years]
Overall Survival
Incidence of Adverse Events [Study start date to study end date, or death, whichever comes first, up to 4 years]
infection, blood transfusion, and other toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, 59 > =Age (years) >= 18;
Newly diagnosed as AML patients according to World Health Organization (WHO) classification;
AML patients meet the adverse risk group according to 2017 European Leukemia Net risk stratification;
Patients have not received prior therapy for AML (except HU);
Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
Liver function: Total bilirubin ≦3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN(except extramedullary infiltration of leukemia)
Renal function：Ccr ≧30 ml/min;
Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.

Exclusion Criteria:

Acute promyeloid leukemia；
AML with central nervous system (CNS) infiltration；
Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
HIV infection;
Patients with severe heart failure (grade 3-4) ;
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Uncontrolled and/or active systemic infection (viral, bacterial or fungal); b) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. c)An active second cancer that requires treatment within 6 months of study entry
Patients deemed unsuitable for enrolment by the investigator;
Patients willing to receive intensive induction chemotherapy
Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen；
Patients reject to participate in the study.