Back to resultsHEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML
Primary Purpose
Leukemia, Acute Myeloid (AML)
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Clifutinib
LoDAC
Azacitidine
Decitabine
Ara-C±IDA
FLAG-IDA
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Acute Myeloid (AML)
Eligibility Criteria
Inclusion Criteria:
- Subject is ≥ 18 years of age at the time of obtaining informed consent.
- Subject has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification;
- Subject is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant )
- Subject is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Subject is eligible for pre-selected salvage chemotherapy at the investigator's discretion
Exclusion Criteria:
- Subject has received prior treatment with other FLT3 inhibitors
- Subject has AML that has relapsed after or is refractory to more than 1 line of therapy
- Subject has an active uncontrolled infection
- Subject is known to have human immunodeficiency virus infection
- Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation
Sites / Locations
- the First Affiliated Hospital,College of Medicine,Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Clifutinib
Salvage Chemotherapy
Arm Description
Subjects received 40 mg dose orally once a day in continuous 28-day cycles, at least 2 hours before and after food. Clifutinib treatment continued until sujects met one of the treatment discontinuation criteria.
Subjects received chemotherapy in 28-day cycles. Subjects on Low-Dose Cytarabine (LoDAC) received 10 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10~14 days. Subjects on azacitidine received 75 mg/m^2 daily by SC for 7 days. Subjects on decitabine received 20 mg/m^2 daily by IV injection for 5 days. Subjects on LoDAC or azacitidine or decitabine treatment continued until they met discontinuation criteria. Subjects on Ara-C±IDA chemotherapy received cytarabine 1~3 g/m^2 daily by IV for 3 days and idarubicin 10 mg/m^2 daily by IV for 3 days. Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC for 6 days (days 1-6), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 1~2 g/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Subjects receiving Ara-C±IDA or FLAG-IDA received 1 cycle of therapy and were assessed for response on day 28+/-2 days.
Outcomes
Primary Outcome Measures
OS
Overall survival was defined as the time from the date of randomization until the date of death from any cause
CR/CRh rate
The CR/CRh rate was defined as the number of subjects who achieved either CR or CRh at any of the postbaseline visits divided by the number of subjects in the analysis population
Secondary Outcome Measures
EFS
EFS was defined as the time from the date of randomization until the date of documented relapse, treatment failure, new anti-leukemia therapy or death from any cause
CR rate
The CR rate was defined as the number of subjects who achieved the best response of CR divided by the number of subjects in the analysis population
CRc Rate
CRc rate was defined as the number of subjects who achieved the best response of CRc (CR, CRh or CRi divided by the number of subjects in the analysis population
Adverse Events
Number of Participants With Adverse Events
Full Information
NCT ID
NCT05586074
First Posted
October 14, 2022
Last Updated
March 20, 2023
Sponsor
Sunshine Lake Pharma Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05586074
Brief Title
HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML
Official Title
HEC73543 Versus Salvage Chemotherapy in Relapsed or Refractory FLT3-ITD Acute Myeloid Leukemia: a Multicenter, Open-label, Randomized Phase 3 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2023 (Actual)
Primary Completion Date
February 10, 2026 (Anticipated)
Study Completion Date
May 14, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunshine Lake Pharma Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A randomized，multicenter, open-label Phase III, clinical study is conducted to evaluate the clinical benefit Clifutinib in Chinese patients with relapsed/ refractory (R/R) FLT3-mutated AML as shown with overall survival compared to salvage chemotherapy, and also to investigate the efficacy of Clifutinib as assessed by CR/CRh rate in these subjects.
Detailed Description
Subjects who are at least 18 years and above at the time of signing informed consent may participate in this study. Subjects will be randomized in a 2:1 ratio to receive Clifutinib or salvage chemotherapy. Subjects will enter the screening period up to 28 days prior to the start of treatment. Prior to randomization, a salvage chemotherapy regimen will be pre-selected for each subjects; options will include low-dose cytarabine (LoDAC), azacitidine, decitabine, Ara-C±IDA or FLAG±IDA. The randomization will be stratified by response to first-line therapy and pre-selected salvage chemotherapy. Participants will be administered treatment over continuous 28-day cycles.
After treatment discontinuation, participants will have a end-of-treatment visit within 7 days after treatment discontinuation, followed by a 30-day follow-up for safety. After that, long term follow-up will be done every 90 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Myeloid (AML)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
324 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Clifutinib
Arm Type
Experimental
Arm Description
Subjects received 40 mg dose orally once a day in continuous 28-day cycles, at least 2 hours before and after food. Clifutinib treatment continued until sujects met one of the treatment discontinuation criteria.
Arm Title
Salvage Chemotherapy
Arm Type
Active Comparator
Arm Description
Subjects received chemotherapy in 28-day cycles. Subjects on Low-Dose Cytarabine (LoDAC) received 10 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10~14 days. Subjects on azacitidine received 75 mg/m^2 daily by SC for 7 days. Subjects on decitabine received 20 mg/m^2 daily by IV injection for 5 days. Subjects on LoDAC or azacitidine or decitabine treatment continued until they met discontinuation criteria. Subjects on Ara-C±IDA chemotherapy received cytarabine 1~3 g/m^2 daily by IV for 3 days and idarubicin 10 mg/m^2 daily by IV for 3 days. Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC for 6 days (days 1-6), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 1~2 g/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Subjects receiving Ara-C±IDA or FLAG-IDA received 1 cycle of therapy and were assessed for response on day 28+/-2 days.
Intervention Type
Drug
Intervention Name(s)
Clifutinib
Other Intervention Name(s)
HEC73543
Intervention Description
tablet, oral
Intervention Type
Drug
Intervention Name(s)
LoDAC
Other Intervention Name(s)
Low Dose Cytarabine
Intervention Description
subcutaneous (SC) or intravenous (IV) injection
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
SC or IV
Intervention Type
Drug
Intervention Name(s)
Decitabine
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
Ara-C±IDA
Other Intervention Name(s)
Cytarabine, Idarubicin
Intervention Description
SC and IV
Intervention Type
Drug
Intervention Name(s)
FLAG-IDA
Other Intervention Name(s)
Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin
Intervention Description
SC and IV
Primary Outcome Measure Information:
Title
OS
Description
Overall survival was defined as the time from the date of randomization until the date of death from any cause
Time Frame
From the date of randomization until the date of death from any cause, assessed up to 5 years
Title
CR/CRh rate
Description
The CR/CRh rate was defined as the number of subjects who achieved either CR or CRh at any of the postbaseline visits divided by the number of subjects in the analysis population
Time Frame
From randomization until the data cut-off date of April 2025, all subjects included in the primary analysis of CR/CRh rate were followed up at least 4 months
Secondary Outcome Measure Information:
Title
EFS
Description
EFS was defined as the time from the date of randomization until the date of documented relapse, treatment failure, new anti-leukemia therapy or death from any cause
Time Frame
From randomization until the data cut-off date of June 2026, median time of follow-up for OS was 15 months
Title
CR rate
Description
The CR rate was defined as the number of subjects who achieved the best response of CR divided by the number of subjects in the analysis population
Time Frame
From randomization until the data cut-off date of June 2026, all subjects included in the analysis of CR rate were followed up at least 4 months
Title
CRc Rate
Description
CRc rate was defined as the number of subjects who achieved the best response of CRc (CR, CRh or CRi divided by the number of subjects in the analysis population
Time Frame
From randomization until the data cut-off date of June 2026, all subjects included in the analysis of CRc rate were followed up at least 4 months
Title
Adverse Events
Description
Number of Participants With Adverse Events
Time Frame
From ICF signature date up to 30 days after the last dose of study drug, median treatment duration for Clifutinib was 140 days versus salvage chemotherapy 140 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is ≥ 18 years of age at the time of obtaining informed consent.
Subject has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification;
Subject is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant )
Subject is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Subject is eligible for pre-selected salvage chemotherapy at the investigator's discretion
Exclusion Criteria:
Subject has received prior treatment with other FLT3 inhibitors
Subject has AML that has relapsed after or is refractory to more than 1 line of therapy
Subject has an active uncontrolled infection
Subject is known to have human immunodeficiency virus infection
Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lejie Zheng, MSc
Phone
86 18511702129
Email
zhenglejie@hec.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD, PhD
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
the First Affiliated Hospital,College of Medicine,Zhejiang University
City
Hanzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin, Doctor
Phone
0571-87236685
Email
jiej0503@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML
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