Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00025662
Status:
COMPLETED
Last Update Posted:
2016-10-28
First Post:
2001-10-11
Brief Title:
Selective T-Cell Depletion to Reduce GVHD Patients Receiving Stem Cell Tx to Treat Leukemia Lymphoma or MDS
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Ex Vivo Selective Depletion of Alloreactive Donor T-Lymphocytes Using RFT5-SMPT-dgA Reducing GVHD Risk Associated With Matched Nonmyeloablative Stem Cell Transplant for Hematologic Malignancies in Older Adults
Status:
COMPLETED
Status Verified Date:
2016-09
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 lymphocytes have undergone selective depletion Certain patients with cancers of the blood undergo transplantation of donated stem cells to generate new and normally functioning bone marrow In addition to producing the new bone marrow the donors T-lymphocytes also fight any tumor cells that might have remained in the body This attack on tumor cells is called a graft-versus-leukemia GVL effect However another type of T-lymphocyte from the donor may cause what is called graft-versus-host-disease GVHD in which the donor cells recognize the patients cells as foreign and mount an immune response to reject them Selective depletion is a technique that was developed to remove the T-lymphocytes that cause harmful GVHD while keeping those that produce the desirable GVL effect
Detailed Description:
Despite improved prophylaxis and treatment graft-versus-host disease GVHD remains a major complication after allogeneic stem cell transplantation Although the most effective way to prevent GVHD is T cell depletion this process results in poor immune function leading to increased rates of relapse graft rejection and post-transplant infections Ideally a method of removing GVHD- producing effector cells while retaining a broad T cell repertoire including preservation of 3rd party antiviral and anti-tumor responses would be desirable Preclinical studies from our lab have demonstrated that alloreactive T cells can be selectively removed from the donor lymphocyte pool in vitro with the use of a specific immunotoxin directed against the interleukin-2 receptor
To test this clinically we will perform nonmyeloablative allogeneic stem cell transplants in older patients with hematologic malignancies Although these patients can be cured with this approach they have significant morbidity and mortality from GVHD At our institution nonmyeloablative transplantation is associated with an incidence of grade II-IV acute GVHD of approximately 50 Although well tolerated in younger patients patients over the age of 50 years have a transplant-related mortality TRM of approximately 35 which is mostly related to GVHD Through selective depletion of alloreactive donor lymphocytes we hope to reduce GVHD mortality while preserving the transplant efficacy
Patients receive a reduced intensity preparative regimen followed by a mobilized peripheral blood stem cell allograft from an HLA-identical sibling donor containing selectively-depleted donor lymphocytes To obtain such a graft colony stimulating factor G-CSF-mobilized peripheral blood from the donor undergoes a positive cluster of differentiation CD34 selection followed by a negative T cell selection using the Nexell Isolex 300i system This stem cell-rich T cell-depleted product will contain a CD34 cell dose of at least 5x106kg The unabsorbed fraction remaining after the positive CD34 selection is then co-cultured for 72 hours with irradiated lymphocytes from the patient The immunotoxin RFT5-SMPT-dgA is added during the last 24 hours of culture to remove alloreacting cells The washed T cell product CD3 cell dose of 1-4 x 108kg is cryopreserved Following the preparative regimen the patient receives successive infusions of the stem cell product and selected lymphocytes All patients receive standard post transplant immunosuppression with cyclosporine for a minimum of 30 days followed by dose reduction depending on the degree of donor lymphocyte chimerism
The primary end point of this study is the incidence and severity of acute GVHD We will also examine the incidence of chronic GVHD engraftment degree of donor-host chimerism transplant related morbidity and mortality as well as disease-free and overall survival Stopping rules will minimize the risk of untoward or unexpected side effects
To test this clinically we will perform nonmyeloablative allogeneic stem cell transplants in older patients with hematologic malignancies Although these patients can be cured with this approach they have significant morbidity and mortality from GVHD At our institution nonmyeloablative transplantation is associated with an incidence of grade II-IV acute GVHD of approximately 50 Although well tolerated in younger patients patients over the age of 50 years have a transplant-related mortality TRM of approximately 35 which is mostly related to GVHD Through selective depletion of alloreactive donor lymphocytes we hope to reduce GVHD mortality while preserving the transplant efficacy
Patients receive a reduced intensity preparative regimen followed by a mobilized peripheral blood stem cell allograft from an HLA-identical sibling donor containing selectively-depleted donor lymphocytes To obtain such a graft colony stimulating factor G-CSF-mobilized peripheral blood from the donor undergoes a positive cluster of differentiation CD34 selection followed by a negative T cell selection using the Nexell Isolex 300i system This stem cell-rich T cell-depleted product will contain a CD34 cell dose of at least 5x106kg The unabsorbed fraction remaining after the positive CD34 selection is then co-cultured for 72 hours with irradiated lymphocytes from the patient The immunotoxin RFT5-SMPT-dgA is added during the last 24 hours of culture to remove alloreacting cells The washed T cell product CD3 cell dose of 1-4 x 108kg is cryopreserved Following the preparative regimen the patient receives successive infusions of the stem cell product and selected lymphocytes All patients receive standard post transplant immunosuppression with cyclosporine for a minimum of 30 days followed by dose reduction depending on the degree of donor lymphocyte chimerism
The primary end point of this study is the incidence and severity of acute GVHD We will also examine the incidence of chronic GVHD engraftment degree of donor-host chimerism transplant related morbidity and mortality as well as disease-free and overall survival Stopping rules will minimize the risk of untoward or unexpected side effects
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 |
|---|---|---|---|
| 01-H-0162 | OTHER | NIH | None |