Selective Depletion of Alloreacting T Cells Using a Photodepletion Technique to Prevent GVHD After HLA-Matched Peripheral Blood Stem Cell Transplantation for Subjects With Hematologic Malignancies
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on
approaches in transplant techniques designed to decrease graft versus host disease (GVHD),
increase the graft-versus-leukemia (GVL) effect, and/or reduce the risk for post-transplant
graft rejection or disease relapse.
Ex vivo selective depletion of alloreacting T cells, hereafter referred as selective
depletion (SD), represents a translational strategy aiming to reduce severe GVHD whilst
preserving GVL. We found that selectively depleted transplants are safe to administer and
associated with less severe acute GVHD. This protocol is designed to evaluate the safety and
efficacy of photodepletion (PD) as an improved selective depletion procedure in the
HLA-matched peripheral blood stem cell transplant setting and to determine whether
post-transplant immunosuppression with cyclosporine is necessary to prevent severe GVHD
after a photodepleted transplant.
The protocol will accrue subjects ages 18-75 who are diagnosed with a hematological
malignancy where allogeneic stem cell transplantation from an HLA-matched sibling would be
normally indicated. Diagnostic categories will include acute and chronic leukemias,
myelodysplastic syndromes, B-cell lymphomas, multiple myeloma, and myeloproliferative
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine
and total body irradiation, followed by an infusion of a stem cell product prepared using
the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been
selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will
receive a lower dose of irradiation to reduce the regimen intensity.
To determine appropriate level of post transplant immunosuppression, we will utilize a three
sequential de-escalation stage design involving 17 subjects per cohort (minimum 17, maximum
51 total evaluable subjects in study). Stopping rules for non-relapse mortality in each
cohort will determine whether to continue to the next stage; to continue accumulating
subjects at the same level; or to stop the protocol.
Cohort 1: Low dose cyclosporine until day 90 then dose tapered to stop within 2 weeks.
Cohort 2: If no severe GVHD is encountered in Cohort 1, the cyclosporine withdrawal will
begin on day 45.
Cohort 3: If no severe GVHD is encountered in Cohort 2, cyclosporine will not be used in the
Primary endpoints will be the incidence of acute grade III/IV GVHD at day 90. Secondary
endpoints will be standard transplant outcome variables: toxicity, non relapse mortality and
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the rate of severe acute GVHD (grade III/IV) after matched sibling transplantation followed by low-dose or no immunosuppression.
Minocher M Battiwalla, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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