Actively Recruiting
Immunosuppression-free Regulatory T-cell Graft-engineered Haploidentical Hematopoietic Cell Transplantation for Relapsed/Refractory and Ultra-High-risk AML/MDS
Led by Dana-Farber Cancer Institute · Updated on 2025-10-20
30
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of an immunosuppression-free regulatory T-cell graft-engineered haploidentical hematopoietic stem cell transplant (HSCT) method in people with relapsed or refractory and ultra-high risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The study aims to reduce the risk of disease relapse and prevent common transplant complications such as graft-versus-host disease (GVHD), which occurs when donor immune cells attack the recipient's tissues. This is a Phase 1 pilot study supported by Dana-Farber Cancer Institute and Regeneron Pharmaceuticals, involving about 30 participants. Participants receive a conditioning regimen that includes radiation (either Total Myeloid and Lymphoid Irradiation or Total Body Irradiation) combined with chemotherapy drugs such as Fludarabine, Thiotepa, Cyclophosphamide, Mesna, and Melphalan depending on the cohort and intensity of treatment. On specific days before transplant, participants are given infusions of Treg-enriched donor cells (the experimental therapy), unmodified donor T cells including cancer-fighting T effector cells, and a transplant of CD34+ haploidentical peripheral blood stem cells. The treatment schedules vary slightly among three cohorts based on disease status and risk classification. During the study, participants are closely monitored with assessments at several time points up to one year post-transplant. These include evaluations for minimal residual disease (MRD), GVHD, and overall health status. The study tracks dose-limiting toxicities, engraftment rates, graft failure, survival rates, and relapse occurrences. Participants undergo various tests and follow-up visits to assess treatment effects and safety, with the total participation lasting about one year after transplantation.
CONDITIONS
Brief Title
IS-free Treg HaploHCT
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed relapsed/refractory AML or MDS with specified blast counts or ultra-high-risk AML/MDS with mutated TP53 as defined by 2022 classification
- Available haploidentical HLA-matched related donor aged 18 to 65 years
- Age 18 to 65 years for Cohorts A and B; age 18 to 75 years for Cohort C
- ECOG performance status 0 to 2
- Adequate pulmonary, cardiac, hepatic, and renal function as specified
- Agreement to use contraception during the study for men and women of childbearing potential
- Ability to provide informed consent
You will not qualify if you...
- Cytotoxic chemotherapy or radiotherapy within 2 weeks (4 weeks for certain drugs) before study start
- Unresolved significant toxicities from prior anti-cancer therapy (except alopecia) unless cleared
- Prior therapies linked to increased risk of liver veno-occlusive disease or known active VOD
- Use of other investigational agents within 21 days before study entry unless cleared
- Presence of extramedullary disease in immune privileged sites (e.g., CNS, testes, eye)
- Recent myocardial infarction, stroke, or thromboembolic events within specified timeframes unless approved
- History of significant gastrointestinal bleeding or thrombotic microangiopathy
- Known donor-specific antibodies requiring depletion
- Inability to withhold interacting medications during conditioning
- Uncontrolled infections
- Prior hematopoietic or solid organ transplantation
- Conditions precluding myeloablative radiation use
- HIV infection on combination therapy
- Hepatitis B or C seropositivity
- Psychiatric or social conditions limiting compliance
- Pregnancy or breastfeeding
- History of other malignancies within 5 years except specified low-risk cases
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 15 days
Participants receive conditioning chemotherapy and radiation, followed by infusions of Treg-enriched donor cells and unmodified donor T cells, culminating with the CD34+ haplo peripheral blood stem cell transplantation.
Multiple infusions and assessments from Day -15 to Day 0
Duration - 12 months
Participants are monitored for graft-versus-host disease, minimal residual disease, and other outcomes for 1 year after transplantation.
Visits on Days 30, 60, 100, 180, and 365 post-transplant
Trial Site Locations
Total: 1 location
1
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Actively Recruiting
Research Team
J
John Koreth, MBBS, DPhil
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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