Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T Cell Depletion, Followed by Delayed T Cell Add-Back
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on
transplant techniques designed to decrease graft versus host disease (GVHD), increase the
graft-versus-leukemia (GVL) effect and reduce the risk of post-transplant graft rejection.
We have found that by controlling the stem cell (CD34+ cell) and T lymphocyte (CD3+ cell)
dose severe GVHD can be reduced whilst beneficial GVL effects can be preserved by postponed
donor lymphocyte infusion (DLI). We found that T cell depleted transplants using the
Nexell/Baxter Isolex 300i system to obtain high CD34+ doses depleted of lymphocytes were
safe to administer and associated with less severe acute GVHD and promising response rates
and overall survival, when combined with a delayed T cell add-back (DLI). This protocol is
designed to evaluate safety and efficacy of an improved T cell depletion procedure using the
Miltenyi CliniMACs system (CD34 reagent system) with a delayed T cell add back in the
HLA-matched peripheral blood stem cell transplant setting.
The protocol will accrue up to 68 subjects ages 10-75 with a hematological malignancy, in
whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely
indicated. 68 sibling donors will also be recruited. Diagnostic categories will include
acute and chronic leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma and
myeloproliferative syndromes.
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 delayed T-cell add back as donor
lymphocyte infusion (DLI) at day 90. Older subjects will receive a lower dose of
irradiation to reduce the regimen intensity.
Primary endpoint will be overall survival at day +200. Non-relapse mortality at day +200
will be monitored for safety. Secondary endpoints will be standard transplant outcome
variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD
and relapse of disease.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Increased rate of survival at day +200. Non-relapse mortality at day +200 will be monitored for safety.
Day 200
Yes
Minocher M Battiwalla, M.D.
Principal Investigator
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
060248
NCT00378534
September 2006
August 2014
Name | Location |
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National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |