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RecruitingNCT04678401

IS-free Treg HaploHCT

A Pilot/Phase 1 Study of Immunosuppression-free Regulatory T-cell Graft-engineered Haploidentical Hematopoietic Cell Transplantation in Relapsed/Refractory and Ultra-High-risk AML/MDS

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
30 (estimated)
Sponsor
Dana-Farber Cancer Institute · Academic / Other
Sex
All
Age
18 Years – 75 Years
Healthy volunteers
Not accepted

Summary

This research study is evaluating the safety and efficacy of the IS-free Treg-cell graft-engineered haplo transplant method in people with relapsed/refractory and Ultra-high risk acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) receiving a haploidentical donor allogeneic hematopoietic stem cell transplant (HSCT). The names of the study interventions involved in this study are: * Radiation-Total Myeloid and Lymphoid Irradiation (TMLI) * Chemotherapy (Fludarabine, Thiotepa, Cyclophosphamide plus Mesna) * Infusion of haplo Treg-enriched donor cells (experimental therapy) * Infusion of unmodified haplo donor T cells (includes cancer-fighting T effector cells) * Infusion of haplo donor CD34+ Peripheral Blood Stem Cells

Detailed description

This study is assessing whether the IS-free Treg-cell graft-engineered haplo HSCT approach will reduce risk of relapse while preventing usual toxicities related to stem cell transplants (e.g., graft-versus-host-disease (GVHD)). GVHD is a complication of transplantation where the T cells (a type of white blood cell that helps protect the body from relapse by killing cancer cells) in the donor graft attack and damage some of the host tissues. Patients who receive an allogeneic (using another person as the donor) hematopoietic stem cell transplant (HSCT) may develop graft-versus-host disease (GVHD) toxicity and are also at risk of disease relapse. The research study procedures include the following: screening for eligibility, study treatment, and follow up visits. Participants will receive the study intervention Treg-enriched donor cells and will then be followed for 1 year after transplantation. It is expected that about 30 people will take part in this research study. Dana-Farber Cancer Institute research funds along with charitable donations are supporting this research study. Regeneron Pharmaceuticals, Inc. (a pharmaceutical company) supported this research study by providing funding and support for correlative laboratory tests.

Conditions

Interventions

TypeNameDescription
RADIATIONRadiationFor MAC regimen: Total Myeloid and Lymphoid Irradiation (TMLI) delivered through Radiation Oncology institutional standards and comprised of 13.5 Gy TMI (9 fractions, 1.5 Gy per fraction, 2 fractions per day) and 11.7 Gy TLI (9 fractions, 1.3 Gy per fraction, 2 fractions per day). OR Total Body Irradiation (TBI) comprised of 12 Gy (6 fractions, 2 Gy per fraction, 2 fractions per day) For RIC regimen: TBI comprised of 2 Gy in 1 fraction.
DRUGFludarabineFor MAC regimen: 30 mg/m\^2/d in 100 ml normal saline (NS) will be administered as a bolus infusion administered by IV infusion over approximately 30 minutes for 5 days (on day -10, -9, -8, -7, -6) For RIC regimen: 40 mg/m\^2/d in 100 ml NS will be administered as a bolus by IV infusion over approximately 30 minutes for 4 days (on day -10, -9, -8, -7)
DRUGThiotepaFor MAC regimen: 3.75 mg/kg diluted in NS to a final concentration of 1mg/mL will be administered by IV infusion over approximately 4 hours daily for 2 days (on day -10, -9) For RIC regimen: 5 mg/kg diluted in NS to a final concentration of 1mg/mL will be administered by IV infusion over approximately 4 hours twice daily for 1 day (on day -11)
DRUGCyclophosphamideFor MAC regimen only: 15 mg/kg diluted in NS per institutional standard and will be administered by IV over 1 hour or as directed per institutional standard practice, daily on D-8, -7.
DRUGMesnaFor MAC regimen only: 3.75mg/kg (25% of cyclophosphamide dose) diluted in 50 mL NS and administered IV over 30 min, will be infused starting 30 min prior to cyclophosphamide and for 3 doses thereafter, at 3, 6 and 9h after cyclophosphamide
BIOLOGICALTreg-enriched donor cellTarget 'Treg-enriched' cell dose is 1-2 x 10\^6 cells/kg. Cells will be given intravenously on Day -4. The day -1 calculated unmodified PBMC T ('Teff') cell dose will be adjusted to maintain a targeted cell ratio of 2 'Treg-enriched' cells:1 'Teff' cell.
BIOLOGICALUnmodified donor T CellUnmodified donor PBMCs will be infused at a calculated 'Teff' dose of 1x10\^6 CD3+ T cells/kg, adjusted per the caveats below: A) If the 'Treg-enriched' product infused was at target dose of 2x106 cells/kg but had ≥30% CD4+CD25+CD127hi cells, the unmodified 'Teff' (calculated) cell dose infused on day -1 will be halved to 0.5x10\^6 CD3+ T cells/kg. B) If the 'Treg-enriched' product was in the range of 1-2x106 cells/kg, the unmodified 'Teff' (calculated) cell dose on day -1 will be adjusted to between 0.5-1x10\^6 CD3+ T cells/kg, dosed to maintain a 2 'Treg-enriched':1 'Teff' (calculated) ratio of infused cells. C) If the 'Treg-enriched' product infused met both caveats A and B above, the unmodified 'Teff' (calculated) cell dose infused on day -1 will be halved to 0.5x10\^6 CD3+ T cells/kg.
PROCEDURECD34+ Haplo Peripheral Blood Stem CellThe megadose donor CD34+ PBSC infusion target is \>10x10\^6 CD34+ cells/kg (ABW or IBW, whichever is greater). If the CD34+ graft has \<6x10\^6 CD34+ cells/kg (ABW or IBW, whichever is greater) (below megadose minimum) it WILL be infused in order to rescue recipient hematopoiesis, and the patient will remain on study.
DRUGMelphalanFor RIC regimen only: 100 mg/m2 will be administered as a bolus by IV infusion over approximately 30 minutes for 1 day (on day -6)

Timeline

Start date
2021-01-12
Primary completion
2028-08-31
Completion
2029-08-31
First posted
2020-12-22
Last updated
2025-10-20

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04678401. Inclusion in this directory is not an endorsement.