Donor-derived γδ T cell therapy for MRD-positive AML after stem-cell transplant

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)

This trial tests whether giving donor-derived γδ T cells can help adults with MRD-positive AML after an allogeneic stem-cell transplant.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT07126782 on ClinicalTrials.gov

What this trial studies

This single-center, randomized, open-label Early Phase I trial gives ex-vivo expanded allogeneic γδ T cells to adults with MRD-positive AML following allo-HSCT. Participants are randomized to one of two infusion dose levels (2E8 cells/kg or 4E8 cells/kg) and are closely monitored for safety and changes in MRD. Eligible patients are adults classified as favorable-to-intermediate risk by 2022 ELN who are MRD-positive by flow cytometry or PCR, have inactive GVHD, ECOG 0–2, and adequate marrow and organ function. The trial’s primary focus is early safety and signals of anti-leukemia activity to guide future larger studies.

Who should consider this trial

Good fit: Adults (≥18 years) with AML who are MRD-positive after allo-HSCT, classified as favorable-to-intermediate risk per 2022 ELN, with inactive GVHD, ECOG 0–2, and adequate blood counts and organ function.

Not a fit: Patients with active or moderate-to-severe GVHD, high-risk AML, inadequate marrow reserve or significant organ dysfunction, or those who are MRD-negative are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could help clear measurable residual disease and lower the risk of AML relapse after transplant.

How similar studies have performed: Early-phase studies of γδ T cells have reported acceptable safety and some anti-leukemia signals, but use of allogeneic γδ cells after allo-HSCT is still novel and not yet proven.

Eligibility criteria

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.

Where this trial is running

Beijing

• Institute of Hematology & Blood Diseases Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Erlie Jiang, M.D.;Ph.D

Conditions AML