Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001873
Status:
COMPLETED
Last Update Posted:
2018-09-26
First Post:
1999-11-03
Brief Title:
The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers
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 - Role of Cyclosporine
Status:
COMPLETED
Status Verified Date:
2017-06-13
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:
Cancers of the blood sometimes referred to as hematologic malignancies are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms The disease is life threatening because it blocks the normal function of the marrow which is to produce red cells preventing anemia white cells preventing infection and platelets preventing progression
Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies However BMT is a complicated procedure and can be associated with dangerous side effects
In this study researchers are attempting to find ways to reduce the complications of BMT so that it would be possible to use it more safely and can be offered more patients In order to do this researchers are developing new techniques to make BMT safer It requires making small changes to the standard procedure which may improve the outcome
The experimental procedures researchers are evaluating are
1 TABT-cell depleted peripheral blood progenitor cell PBPC transplantation
2 TAB Cyclosporine given immediately after the transplant
3 TABAdd-back of donor lymphocytes
Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies
Bone marrow transplants are a potential form of therapy for patients with hematologic malignancies However BMT is a complicated procedure and can be associated with dangerous side effects
In this study researchers are attempting to find ways to reduce the complications of BMT so that it would be possible to use it more safely and can be offered more patients In order to do this researchers are developing new techniques to make BMT safer It requires making small changes to the standard procedure which may improve the outcome
The experimental procedures researchers are evaluating are
1 TABT-cell depleted peripheral blood progenitor cell PBPC transplantation
2 TAB Cyclosporine given immediately after the transplant
3 TABAdd-back of donor lymphocytes
Patients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies
Detailed Description:
Bone marrow 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 A CD34 stem cell dose of greater than 3 x 106kg was found to increase survival and reduce relapse while a CD3 lymphocyte dose of less than 1 x 105kg was associated with a very low incidence of GVHD Although processing of 2 peripheral blood progenitor cell PBPC collections with the CellPro immunoabsorption method combined CD34-positive selection and CD2-negative selection provided an improvement over previous methods the system did not always achieve these optimal cell doses A recent preclinical evaluation by the Department of Transfusion Medicine of a new immunomagnetic cell selection system available from Nexell Inc has demonstrated improved recovery of CD34 cells and increased depletion of T lymphocytes compared to the CellPro method Incorporation of the Nexell system Isolex 300i into this clinical protocol will allow us to more consistently achieve CD34 cell doses above the threshold of 3 x 106kg and CD3 lymphocyte dosing in the region of 05 x 105kg This will make it possible to test 1 the potential benefit of optimized transplant cell doses 2 elimination of post transplant immunosuppression to enhance immune recovery
In this study we will use the Nexell Isolex 300i system to obtain more data on the relationship between CD34 stem cell dose and outcome In recipients who receive a T cell dose less than 05 x 105 CD3 cellskg the effect of withdrawing cyclosporine on development of GVHD will be evaluated in a cohort study 20 patients will receive low dose cyclosporine If the incidence of grade II or worse GVHD is 10 or less no post transplant immunosuppression will be given to the next cohort and the incidence and severity of acute GVHD again assessed Stopping rules for unacceptable GVHD severity will be applied Two match groups HLA 66 and 56 donor-recipient pairs will be separately studied using this approach
In a second phase of the study we will continue to accumulate data on T lymphocyte add-back given on day 45 and day 100 after transplant For this phase cyclosporine will be reintroduced on day 44 and continued until day 120 to accelerate immune recovery
Up to 70 patients aged between 10 and 55 years will be studied in each subset HLA 66 and 56 matched cohorts The major endpoint of the study is acute GVHD after transplant We will also measure engraftment acute and chronic GVHD leukemic relapse transplant-related and all causes of mortality cytomegalovirus reactivation and leukemia-free survival Patients will be followed for a minimum of 5 years
In this study we will use the Nexell Isolex 300i system to obtain more data on the relationship between CD34 stem cell dose and outcome In recipients who receive a T cell dose less than 05 x 105 CD3 cellskg the effect of withdrawing cyclosporine on development of GVHD will be evaluated in a cohort study 20 patients will receive low dose cyclosporine If the incidence of grade II or worse GVHD is 10 or less no post transplant immunosuppression will be given to the next cohort and the incidence and severity of acute GVHD again assessed Stopping rules for unacceptable GVHD severity will be applied Two match groups HLA 66 and 56 donor-recipient pairs will be separately studied using this approach
In a second phase of the study we will continue to accumulate data on T lymphocyte add-back given on day 45 and day 100 after transplant For this phase cyclosporine will be reintroduced on day 44 and continued until day 120 to accelerate immune recovery
Up to 70 patients aged between 10 and 55 years will be studied in each subset HLA 66 and 56 matched cohorts The major endpoint of the study is acute GVHD after transplant We will also measure engraftment acute and chronic GVHD leukemic relapse transplant-related and all causes of mortality cytomegalovirus reactivation and leukemia-free survival Patients will be followed for a minimum of 5 years
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 |
|---|---|---|---|
| 99-H-0046 | None | None | None |