AML, AML (Acute Myelogenous Leukemia)
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of allogeneic γδ T cells in patients with MRD-positive AML after allo-HSCT.
Detailed description
This is a single-center, randomized, open label phase I clinical trial to evaluate the efficacy and safety of ex-vivo expanded allogeneic γδ T cells in patients with MRD-positive AML after allo-HSCT. The infusion doses of γδ T cells were 2E8 cells/kg and 4E8 cells/kg.
Interventions
BIOLOGICALEx-vivo expanded allogeneic γδ T cells
Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδ T cells from donors will be adoptively transfused.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study. 2. Age≥18 years old, gender unlimited. 3. All the subjects met the 2016 WHO classification and were diagnosed with AML via MICM (Morphology,Immunophenotyping, Cytogenetics, and Molecular genetics). 4. AML patients receiving allo-HSCT. 5. Subjects classified into the favorable -to-intermediate risk group according to the 2022 European Leukemia Net (ELN) risk stratification guidelines. 6. All subjects were detected positive for MRD, and MRD was positive by flow cytometry (MFC) or/and positive for fusion genes/gene mutations by RQ-PCR. 7. ECOG performance status score: 0-2. 8. Inactive GVHD (acute GVHD grade II-IV or moderate to severe chronic GVHD). 9. Adequate bone marrow reserve, defined as: absolute neutrophil count (ANC) \> 0.5E9/L and platelet count ≥20E9/L. 10. Adequate organ function as per protocol. 11. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 28 days post study.
Exclusion criteria
1. Post-transplant relapse or extramedullary disease: AML patients post-allo-HSCT with ≥5% blasts in peripheral blood or bone marrow (excluding causes such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia infiltration. 2. Active GVHD: Subjects with active GVHD within 30 days before screening. 3. Active infections: HBV, HCV, HIV, syphilis (TP), active CMV, or EBV infection. 4. Neurological disorders: active autoimmune or inflammatory neurological diseases, clinically significant active cerebrovascular disease. 5. Unstable systemic diseases, including: unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months before screening), myocardial infarction (within 6 months before screening), NYHA Class III/IV heart failure, refractory hypertension (defined as failure to control blood pressure despite lifestyle modifications and treatment with ≥4 antihypertensive drugs, including diuretics, for \>1 month), clinically significant arrhythmias requiring medication, severe hepatic, renal, or metabolic disorders. 6. Major surgery: Subjects who underwent major surgery within 4 weeks before screening, as deemed ineligible by the investigator. 7. Concurrent non-hematologic malignancies. 8. Cardiac abnormalities, meeting any of the following: Left ventricular ejection fraction (LVEF) ≤45%. NYHA Class III/IV congestive heart failure. QTc interval \>480 msec. Other cardiac conditions considered unsuitable by the investigator. 9. History of epilepsy or other active CNS disorders. 10. Uncontrolled infections: active systemic infections requiring treatment (e.g., sepsis, bacteremia, fungemia, tuberculosis, opportunistic infections). 11. Recent participation in other interventional trials: Subjects who participated in another interventional clinical study within 30 days prior to enrollment. 12. Other conditions: Any other circumstances deemed by the investigator to compromise subject safety or trial integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 4weeks | Defined as the MRD-negative complete remission rate (CRMRD- rate) at 4 weeks, representing the proportion of subjects achieving MRD negativity after 4 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRD-negative rate at 2 weeks (CRMRD- rate) | 2weeks | Proportion of subjects achieving MRD negativity after 2 weeks of treatment. |
| Duration of Response (DOR) | 4weeks | Time from the first documented MRD-negative complete remission (CRMRD-) to the first occurrence of disease progression or death from any cause. For subjects without confirmed progression or death, DOR will be censored at the last evaluable assessment. |
| 2-Year Overall Survival (OS) | 2 years | Proportion of subjects who remain alive at 2 years from the first dose of study treatment. |
| Safety observation | Baseline to 2 years | Incidence of Grade ≥3 adverse events (AEs) Incidence of GVHD Non-relapse mortality (NRM) |
Countries
China
Contacts
Primary ContactErlie Jiang, M.D.;Ph.D
Outcome results
None listed