Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00061581
Status:
COMPLETED
Last Update Posted:
2018-09-26
First Post:
2003-05-29
Brief Title:
Experimental Bone Marrow Transplant Protocol
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2017-06-14
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
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 104kg 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 1022 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
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 104kg 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 1022 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-H-0192 | None | None | None |