The Efficacy and Safety Assessment of Allogeneic γδ T Cells in Patients With MRD-positive AML After Allo-HSCT

Official title

Clinical Study on the Efficacy and Safety of Allogeneic γδ T Cells in the Treatment of Patients With MRD-positive Acute Myeloid Leukemia (AML) After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Overview

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

• Biological Ex-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.

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: 4weeks]

Secondary outcome measures (4)

• MRD-negative rate at 2 weeks (CRMRD- rate) [Time frame: 2weeks]
• Duration of Response (DOR) [Time frame: 4weeks]
• 2-Year Overall Survival (OS) [Time frame: 2 years]
• Safety observation [Time frame: Baseline to 2 years]

Eligibility criteria

Inclusion criteria

• Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
• Age≥18 years old, gender unlimited.
• All the subjects met the 2016 WHO classification and were diagnosed with AML via MICM (Morphology,Immunophenotyping, Cytogenetics, and Molecular genetics).
• AML patients receiving allo-HSCT.
• Subjects classified into the favorable -to-intermediate risk group according to the 2022 European Leukemia Net (ELN) risk stratification guidelines.
• 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.
• ECOG performance status score: 0-2.
• Inactive GVHD (acute GVHD grade II-IV or moderate to severe chronic GVHD).
• Adequate bone marrow reserve, defined as: absolute neutrophil count (ANC) > 0.5E9/L and platelet count ≥20E9/L.
• Adequate organ function as per protocol.
• 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

• 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.
• Active GVHD: Subjects with active GVHD within 30 days before screening.
• Active infections: HBV, HCV, HIV, syphilis (TP), active CMV, or EBV infection.
• Neurological disorders: active autoimmune or inflammatory neurological diseases, clinically significant active cerebrovascular disease.
• 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.
• Major surgery: Subjects who underwent major surgery within 4 weeks before screening, as deemed ineligible by the investigator.
• Concurrent non-hematologic malignancies.
• 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.
• History of epilepsy or other active CNS disorders.
• Uncontrolled infections: active systemic infections requiring treatment (e.g., sepsis, bacteremia, fungemia, tuberculosis, opportunistic infections).
• Recent participation in other interventional trials: Subjects who participated in another interventional clinical study within 30 days prior to enrollment.
• Other conditions: Any other circumstances deemed by the investigator to compromise subject safety or trial integrity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Hematology & Blood Diseases Hospital — Beijing

Identifiers

NCT: NCT07126782 · IIT2025056

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗