Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00079391
Status:
COMPLETED
Last Update Posted:
2015-10-26
First Post:
2004-03-08
Brief Title:
Stem Cell Transplantation and T-Cell Add-Back to Treat Bone Marrow Malignancies
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 Peri-transplant Cyclosporine on Chimerism
Status:
COMPLETED
Status Verified Date:
2014-06
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:
This study will evaluate the safety and effectiveness of stem cell transplantation in which the donors T cells a type of lymphocyte or white blood cell are removed and then added back Certain patients with bone marrow malignancies undergo transplantation of donated stem cells to generate new and normally functioning bone marrow However T-cells from the donor may see the patients cells as foreign and mount an immune response to reject them causing what is called graft-versus-host-disease GVHD Therefore in this protocol T-cells are removed from the donor cells to prevent this complication However because T-cells are important in fighting viral infections as well as any remaining malignant cells called graft-versus-leukemia effect the donor T-cells are given to the patient added back at a later time after the transplant when they can provide needed immunity with less risk of causing GVHD
Patients between 10 and 55 years of age with acute or chronic leukemia myelodysplastic syndrome or myeloproliferative syndrome may be eligible for this study Prospective participants and their donors are screened with a medical history and physical examination blood tests including a test to match for genetic compatibility breathing tests chest and sinus x-rays and tests of heart function They also undergo a bone marrow biopsy and aspiration For this procedure done under local anesthetic about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone
They undergo apheresis to collect lymphocytes for research studies This procedure involves collecting blood through a needle in the arm similar to donating a unit of blood The lymphocytes are then separated and removed by a cell separator machine and the rest of the blood is returned through a needle in the other arm
Before treatment begins patients have a central intravenous line flexible plastic tube placed in a vein in the chest This line remains in place during the stem cell transplant and recovery period for drawing and transfusing blood giving medications and infusing the donated cells Preparation for the transfusion includes high-dose radiation and chemotherapy Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days Eight days before the transplant they begin taking fludarabine and 3 days before the procedure they start cyclophosphamide
Patients between 10 and 55 years of age with acute or chronic leukemia myelodysplastic syndrome or myeloproliferative syndrome may be eligible for this study Prospective participants and their donors are screened with a medical history and physical examination blood tests including a test to match for genetic compatibility breathing tests chest and sinus x-rays and tests of heart function They also undergo a bone marrow biopsy and aspiration For this procedure done under local anesthetic about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone
They undergo apheresis to collect lymphocytes for research studies This procedure involves collecting blood through a needle in the arm similar to donating a unit of blood The lymphocytes are then separated and removed by a cell separator machine and the rest of the blood is returned through a needle in the other arm
Before treatment begins patients have a central intravenous line flexible plastic tube placed in a vein in the chest This line remains in place during the stem cell transplant and recovery period for drawing and transfusing blood giving medications and infusing the donated cells Preparation for the transfusion includes high-dose radiation and chemotherapy Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days Eight days before the transplant they begin taking fludarabine and 3 days before the procedure they start cyclophosphamide
Detailed Description:
Bone marrow stem cell transplant studies carried out by the National Heart Lung Blood Institute NHLBI Bone Marrow Transplantation BMT Unit have focused on approaches to optimize the stem cell and lymphocyte dose in order to improve transplant survival and increase the graft-versus-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 reduced 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 We use 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 is covered by an Investigational Device Exemption A persisting problem with these T cell depleted transplants has been the slow acquisition of full donor T cell engraftment T cell chimerism Two previous protocols have failed to increase the speed of donor T cell chimerism 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 remains an important therapeutic goal In this study we will test whether cyclosporine given between day -6 and 21 after transplant can significantly improve day 30 T cell chimerism the principle end-point The study also will measure the incidence of acute and chronic GVHD day 100 transplant related mortality cytomegalovirus reactivation relapse and disease-free survival with appropriate safety stopping rules
This protocol follows closely previous studies in this series Three additional modifications will be made however 1 The first T cell add-back will be delayed until day 60 instead of day 45 so as to continue to allow a 45 day period without cyclosporine immunosuppression 2 No day 100 T cell add-back will be given In previous studies many patients have for protocol-defined reasons not received the second transfusion and there is no evidence that it is required 3 Patients with high-risk leukemias with a high relapse probability will receive an additional chemotherapy agent prior to transplant using etoposide VP16 60mgkg to improve the chance of remaining in remission
We have found that the outcome from transplant is improved by controlling the stem cell CD34 cell and T lymphocyte CD3 cell dose We use 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 is covered by an Investigational Device Exemption A persisting problem with these T cell depleted transplants has been the slow acquisition of full donor T cell engraftment T cell chimerism Two previous protocols have failed to increase the speed of donor T cell chimerism 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 remains an important therapeutic goal In this study we will test whether cyclosporine given between day -6 and 21 after transplant can significantly improve day 30 T cell chimerism the principle end-point The study also will measure the incidence of acute and chronic GVHD day 100 transplant related mortality cytomegalovirus reactivation relapse and disease-free survival with appropriate safety stopping rules
This protocol follows closely previous studies in this series Three additional modifications will be made however 1 The first T cell add-back will be delayed until day 60 instead of day 45 so as to continue to allow a 45 day period without cyclosporine immunosuppression 2 No day 100 T cell add-back will be given In previous studies many patients have for protocol-defined reasons not received the second transfusion and there is no evidence that it is required 3 Patients with high-risk leukemias with a high relapse probability will receive an additional chemotherapy agent prior to transplant using etoposide VP16 60mgkg to improve the chance of remaining in remission
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 |
|---|---|---|---|
| 04-H-0112 | OTHER | NIH | None |