HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML

Sponsor
Sunshine Lake Pharma Co., Ltd. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05586074
Collaborator
(none)
324
2
41.5

Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
324 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
HEC73543 Versus Salvage Chemotherapy in Relapsed or Refractory FLT3-ITD Acute Myeloid Leukemia: a Multicenter, Open-label, Randomized Phase 3 Trial
Anticipated Study Start Date :
Nov 28, 2022
Anticipated Primary Completion Date :
Feb 10, 2026
Anticipated Study Completion Date :
May 14, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Clifutinib

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.

Drug: Clifutinib
tablet, oral
Other Names:
  • HEC73543
  • Active Comparator: Salvage Chemotherapy

    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.

    Drug: LoDAC
    subcutaneous (SC) or intravenous (IV) injection
    Other Names:
  • Low Dose Cytarabine
  • Drug: Azacitidine
    SC or IV

    Drug: Decitabine
    IV

    Drug: Ara-C±IDA
    SC and IV
    Other Names:
  • Cytarabine, Idarubicin
  • Drug: FLAG-IDA
    SC and IV
    Other Names:
  • Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin
  • Outcome Measures

    Primary Outcome Measures

    1. OS [From the date of randomization until the date of death from any cause, assessed up to 5 years]

      Overall survival was defined as the time from the date of randomization until the date of death from any cause

    2. CR/CRh rate [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]

      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

    1. EFS [From randomization until the data cut-off date of June 2026, median time of follow-up for OS was 15 months]

      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

    2. CR rate [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]

      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

    3. CRc Rate [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]

      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

    4. Adverse Events [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]

      Number of Participants With Adverse Events

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Sunshine Lake Pharma Co., Ltd.

    Investigators

    • Principal Investigator: Jie Jin, MD, PhD, First Affiliated Hospital of Zhejiang University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sunshine Lake Pharma Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT05586074
    Other Study ID Numbers:
    • HEC73543-AML-301
    First Posted:
    Oct 19, 2022
    Last Update Posted:
    Oct 19, 2022
    Last Verified:
    Oct 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 19, 2022