Experimental Bone Marrow Transplant Protocol
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|ClinicalTrials.gov Identifier: NCT00061581|
Recruitment Status : Completed
First Posted : May 29, 2003
Last Update Posted : February 14, 2018
Bone marrow transplantation (BMT) is a risky procedure. If doctors could reduce the complications, BMT would be safer to use for a wider range of conditions. The purposes of this study are
- to prevent graft rejection by increasing the amount of immunosuppression and by giving some lymphocytes from the donor before transplant;
- to prevent graft-versus-host disease (GVHD) by transplanting T-cell depleted stem cells;
- to improve the immune effect against residual leukemia by the add-back of donor lymphocytes before transplant and six or more weeks after transplant.
Beyond the standard transplant protocol, study participants will undergo additional procedures. First, along with total body irradiation, patients will receive two drugs (a high dose of cyclophosphamide and fludarabine) to suppress immunity and prevent rejection of the transplant. Second, four days before the transplant, patients will be given donor lymphocytes that have been irradiated to make them incapable of causing GVHD. On the day of the transplant, patients will receive an infusion of T-cell depleted bone marrow stem cells. Finally, patients will receive two doses of add-back donor T-cells (45 and 100 days post transplant) and the immunosuppressive drug cyclosporine starting on day 44 until about six months after transplant.
Study participants must be between the ages of 10 and 56 and have a family member who is a suitable stem cell donor match.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphocytic Leukemia Chronic Myeloid Leukemia Acute Myelocytic Leukemia Myelodysplastic Syndromes Myeloproliferative Disorders||Device: Isolex 300i Stem Cell Selection||Phase 2|
Stem cell transplant studies carried out by the NHLBI BMT Unit have focused on approaches to optimize the stem cell and lymphocyte dose in order to improve transplant survival and increase the graft-vs.-leukemia effect. The aim is to create the transplant conditions that permit rapid donor immune recovery without causing graft-versus-host disease (GVHD) by using no post-transplant immunosuppression in conjunction with a transplant depleted of T cells to a fixed low dose, below the threshold known to be associated with GVHD.
We have found that the outcome from transplant is improved by controlling the stem cell (CD34+ cell) and T lymphocyte (CD3+ cell) dose. In the last study, in this series, we used the Nexell Isolex 300i system to obtain high CD34+ doses depleted of lymphocytes to a fixed CD3+ T cell dose of 2 x 10(4)/kg. The use of the cell separator and the monoclonal antibodies was covered by IDE 8139. The study measured the incidence of acute GVHD and used chimerism assays to determine the percentage of donor and recipient cells circulating at different time-points after transplant. We found that in the first six weeks donor T cell chimerism varied widely reaching 100% only in 10/22 patients. Thus the goal or rapid donor immune recovery was achievable only in about half the patients. Patients with mixed donor-recipient T cell populations are known to be at higher risk for late graft rejection and leukemic relapse after transplant. Therefore the achievement of full donor chimerism is an important therapeutic goal.
To improve donor T cell chimerism we will test whether the addition of irradiated donor lymphocytes during the preparative regimen of the transplant can increase the chance of achieving 100% donor T cell chimerism within six weeks of transplant. It is known that irradiated lymphocytes do not cause GVHD and that they can suppress residual host immunity, thus promoting donor lymphocyte engraftment. The end point of the study will be the proportion of patients achieving full donor chimerism six weeks after transplant. Apart from this addition of irradiated lymphocytes and some minor modifications, this protocol will be identical to the predecessor protocol 02-H-0111. This involves the continued use of the Isolex 300i cell separator and the monoclonal antibodies provided by CTEP (anti CD 6, anti CD2, anti CD7). This is covered by a continuing IND for the selection of CD34+ and CD3+ cells for T cell depleted peripheral blood stem cell transplantation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T Cell Add-Back for Hematological Malignancies - Effect of Irradiated Donor Lymphocytes on Chimerism|
|Study Start Date :||May 19, 2003|
|Actual Primary Completion Date :||December 28, 2007|
|Actual Study Completion Date :||June 14, 2017|
- Acute and chronic graft-versus-host disease, transplant-related mortality (TRM), overall mortality, leukemic relapse, CMV reactivation and disease, and graft failure.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00061581
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||A. John Barrett, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|