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

Primary Purpose

Acute Myeloid Leukemia, Adult

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
venetoclax combined with decitabine
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia, Adult

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female, 59 > =Age (years) >= 18;
  2. Newly diagnosed as AML patients according to World Health Organization (WHO) classification;
  3. AML patients meet the adverse risk group according to 2017 European Leukemia Net risk stratification;
  4. Patients have not received prior therapy for AML (except HU);
  5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
  6. 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)
  7. Renal function：Ccr ≧30 ml/min;
  8. 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:

  1. Acute promyeloid leukemia；
  2. AML with central nervous system (CNS) infiltration；
  3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
  4. HIV infection;
  5. Patients with severe heart failure (grade 3-4) ;
  6. 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
  7. Patients deemed unsuitable for enrolment by the investigator;
  8. Patients willing to receive intensive induction chemotherapy
  9. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen；
  10. Patients reject to participate in the study.

Sites / Locations

  • The First Affiliated Hospital of Soochow University, Jiangsu Institute of HematologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment regime

Arm Description

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

Outcomes

Primary Outcome Measures

CR/CRi/morphologic leukemia free state (MLFS)
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)
Event Free Survival
Overall Survival(OS)
Overall Survival
Incidence of Adverse Events
infection, blood transfusion, and other toxicity

Full Information

First Posted
February 9, 2021
Last Updated
November 8, 2021
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT04752527
Brief Title
Individualized Induction Therapy for Non-elderly Acute Myeloid Leukemia Patients With Adverse Risk Features
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 20, 2021 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment regime
Arm Type
Experimental
Arm Description
combination of venetoclax plus azacitidine, and Sorafenib for patients with high FLT3-ITD allelic ratio
Intervention Type
Drug
Intervention Name(s)
venetoclax combined with decitabine
Other Intervention Name(s)
combination of venetoclax plus decitabine with or without sorafenib
Intervention Description
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.
Primary Outcome Measure Information:
Title
CR/CRi/morphologic leukemia free state (MLFS)
Description
Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State（after one cycle or two cycles of induction therapy）
Time Frame
Study start date to study end date, or death, whichever comes first, up to 4 years
Secondary Outcome Measure Information:
Title
Event Free Survival(EFS)
Description
Event Free Survival
Time Frame
Study start date to study end date, or death, whichever comes first, up to 4 years
Title
Overall Survival(OS)
Description
Overall Survival
Time Frame
Study start date to study end date, or death, whichever comes first, up to 4 years
Title
Incidence of Adverse Events
Description
infection, blood transfusion, and other toxicity
Time Frame
Study start date to study end date, or death, whichever comes first, up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
suning chen, professor
Phone
8613814881746
Email
chensuning@sina.com
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suning Chen
Phone
13814881746
Email
chensuning@sina.com

12. IPD Sharing Statement

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

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