The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers
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|ClinicalTrials.gov Identifier: NCT00001873|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : October 6, 2017
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:
- <TAB>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation
- <TAB> Cyclosporine given immediately after the transplant
- <TAB>Add-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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia Graft vs Host Disease Hematologic Neoplasm Multiple Myeloma Myelodysplastic Syndrome||Device: Isolex 300i plus MoAbs||Phase 2|
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 10(6)/kg was found to increase survival and reduce relapse, while a CD3+ lymphocyte dose of less than 1 x 10(5)/kg 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 10(6)/kg and CD3+ lymphocyte dosing in the region of 0.5 x 10(5)/kg. 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 0.5 x 10(5) CD3+ cells/kg 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 6/6 and 5/6 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 6/6 and 5/6 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||102 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 - Role of Cyclosporine|
|Study Start Date :||February 22, 1999|
|Actual Primary Completion Date :||December 28, 2007|
|Actual Study Completion Date :||June 13, 2017|
- The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant (and before D45 add-back). [ Time Frame: Day 45 ]
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): NCT00001873
|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)|