Acute Myeloid Leukemia (AML), Allogeneic Hematopoietic Cell Transplantation (HCT), FLT3-ITD Mutation, Gilteritinib, Maintenance Therapy, Sorafenib
Conditions
Keywords
Acute Myeloid Leukemia, FLT3-ITD Mutation, Allogeneic Hematopoietic Cell Transplantatio, Maintenance therapy, Gilteritinib, sorafeni
Brief summary
The study population consisted of FLT3-ITD-mutated AML patients who were FLT3-ITD-positive before allogeneic hematopoietic stem cell transplantation. This open-label, randomized, controlled trial enrolled participants and randomly assigned them in a 1:1 ratio to either the experimental group or the control group. The experimental group received maintenance therapy with gilteritinib, while the control group received maintenance therapy with sorafenib, with 297 cases in each group, totaling 594 enrolled subjects. All patients' minimal residual disease (MRD) testing was sent to the designated central laboratory and uniformly performed using the PCR-NGS method to ensure consistency and comparability of the test results. Study Visits: This study includes a screening period (within 30 days prior to HCT) and a 2-year treatment phase, with efficacy and safety follow-up until death, withdrawal of informed consent, or 2 years after the first administration of treatment, whichever occurs first.
Interventions
DRUGGilteritinib
Randomization should be performed between days 60 and 90 after the day of allogeneic hematopoietic stem cell infusion (day 0 post-HCT). Participants allocated in this arm must take Gilteritinib 3 tablets (40 mg per tablet) daily in the morning, with continuous daily administration.
DRUGSorafenib
Randomization should be performed between days 60 and 90 after the day of allogeneic hematopoietic stem cell infusion (day 0 post-HCT). Participants allocated in this arm must take sorafenib 400 mg orally, twice daily (BID), with continuous administration
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent and willingness to participate in this clinical study; * Gender is not limited, age range is 14-70 years old (including threshold); * ECOG score 0-2 points; * Diagnosed with AML through bone marrow morphology, immunology, cytogenetics, and molecular biology (MICM) typing, and confirmed to have FLT3-ITD mutation; * Successfully accepted allo HSCT, with no restrictions on the pre-treatment protocol, allowing any donor source \[fully matched cell, unrelated donor (URD), incompatible unrelated donor, haploidentical relative donor or umbilical cord blood\], allowing any graft source \[umbilical cord blood, bone marrow (BM), peripheral blood (PB)\]; ⑥ Patients with complete morphological remission (CR) prior to allo HSCT, and FLT3-ITD MRD positivity detected by PCR-NGS within 30 days prior to allo HSCT (defined as FLT3-ITD transcript level ≥ 10 - 6); ⑦ After transplantation: hematopoietic function implantation (ANC ≥ 500/μ L, platelet count ≥ 20000/μ L and not dependent on infusion), oral administration of investigational drugs, exclusion of overlap syndrome, complete donor chimerism (FDC) status, no activity requiring daily prednisone dose\>0.5 mg/kg, acute GVHD; ⑧ Clinical laboratory tests meet the following criteria: a. Serum creatinine ≤ 2.0 times the upper limit of normal value; b. Total bilirubin ≤ 2.5 mg/dL (excluding Gilbert syndrome patients); c. Serum AST and/or ALT\<3 times the upper limit of normal values; ⑨ Maintenance treatment should be started 60 to 90 days after transplantation; ⑩ Female participants must meet the following criteria: have undergone menopause (at least 1 year without menstruation) or surgical sterilization (at least 1 month ago) before screening for infertility; Or have the ability to conceive but agree not to plan pregnancy during the study period and within 6 months after the last dose; Conduct pregnancy tests during the screening period; If there is heterosexual behavior, agree to continue using local standard high-efficiency contraceptive measures plus barrier method from the beginning of screening to 6 months after the last administration; Agree not to breastfeed or donate eggs during the study period and for 6 months after the last administration Male participants must meet the following requirements: male participants (even if sterilized) and their reproductive partners must use efficient contraception plus barrier method during the study period and within 127 days after the last dose; Male participants are not allowed to donate sperm during the study period and for 127 days after the last dose;
Exclusion criteria
* Allergies to Girotinib or Sorafenib, as well as any components of the therapeutic drugs used during the study period; * Any serious comorbidities that make patients unsuitable for participation in this study or may affect protocol compliance; * FLT3-ITD molecular MRD positivity before maintenance therapy; * Severe organ dysfunction such as organ failure occurs after allogeneic hematopoietic stem cell transplantation; * Subjects who are positive for hepatitis B B surface antigen (HBsAg) and whose hepatitis B virus (HBV) DNA titer is higher than the upper limit of the normal value range of the research center, and who are judged by the researchers not suitable for this study; Individuals with positive hepatitis C virus (HCV) antibodies and positive peripheral blood HCV RNA; Individuals who are HIV antibody positive; Positive syphilis test results; ⑥ There is evidence within the first 6 months of enrollment that the patient has other diseases or physiological conditions that may interfere with the evaluation results of this trial, or complications that seriously endanger life, including but not limited to uncontrolled infections, pulmonary arterial hypertension, severe heart failure (NYHA grades III and IV), unstable angina or acute myocardial infarction, poorly controlled refractory hypertension (based on hospitalization medical records diagnosis), etc; ⑦ Individuals with mental or neurological disorders who are unable to express their wishes correctly; ⑧ Individuals who have had active malignant solid tumors within the past 5 years prior to participating in this study, except for cervical cancer, localized prostate cancer in situ, and non melanoma skin cancer that have been cured; ⑨ Have participated in or are currently participating in other clinical trials within one month prior to enrollment; ⑩ Researchers have determined that individuals are not suitable to participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurable residual disease recurrence-free survival (MRD-RFS) | 2-year | The time from randomization to occurrence of hematological recurrence, molecular recurrence (FLT3-ITD mutation MRD changes from negative to positive), or death from any cause (whichever occurs first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Surivival (OS) | 2-year | The time from randomazation to death |
| Molecular Recurrence | 2-year | From random to MRD-positive detected by PCR NGS of FLT3-ITD mutation |
| MFC-MRD Recurrence | 2-year | From randomization to MRD-positive detected by MFC |
| Cumulative Incidence of Relapse (CIR) | 2-year | From randomization to relapse |
| Non-Relapse Mortality (NRM) | 2-year | From randomization to death unrelated to AML |
| Chronic Graft-versus-Host Disease (cGVHD) | 2-year | From randomization to the occurence of chronic graft-versus-host disease (cGVHD) |
| Acute Graft-versus-Host Disease (aGVHD) | 2-year | From randomization to the occurence of acute graft-versus-host disease (aGVHD) |
| Graft-versus-Host Disease and Relapse-free survival (GRFS) | 2-year | From randomization to the occurence of graft-versus-host disease (GVHD), relapse or death, which occurs first |
| Relpase-Free Survival (RFS) | 2-year | From randomization to the occurence of relapse or death, which occurs first |
Countries
China
Contacts
CONTACTJia Chen, MD, PhD
Outcome results
None listed