Ignite Creation Date:
2024-05-05 @ 4:44 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00306332
Status:
TERMINATED
Last Update Posted:
2009-08-18
First Post:
2006-03-22
Brief Title:
T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures
Status:
TERMINATED
Status Verified Date:
2009-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Interim analysis has shown that the objectives of this study can not be reached
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures
Background
Removal of T-cells from the donor graft T-cell depletion offers the possibility for prevention of GVHD and subsequently less transplant related morbidity and mortality after allogeneic stem cell transplantation SCT There are several techniques to deplete T-cells from the stem cell grafts eg physical immunological and combined physical immunological separation methods All these techniques result in a stem cell graft with sufficient CD34 stem cells combined with an adequate depletion of T and B cells CD34 selected stem cell grafts are very pure and do not contain any additional cell populations In contrast CD3CD19 depleted grafts still contain NK-cells monocytes and dendritic cells that are part of the innate immune system Theoreticallythe presence of these cells may positively influence immunological reconstitution and the graft-versus-leukaemia GVL effect respectively resulting in improved outcome after SCT
Objectives
To evaluate the differences in immunological reconstitution transplant related mortality disease-free survival and overall survival after T-cell depleted allogeneic SCT for haematological malignancies using either immunomagnetic CD34 selection or immunomagnetic CD3CD19 depletion using the CliniMACS system in approximately 270 consecutive patients
Additionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution and differences in NK-cell repertoire will be monitored NK-cell mediated anti-tumor reactivity will be monitored in patients transplanted with and without NK-cells in the stem cell graft CD3CD19 depletion versus CD34 selection Secondary objectives are to evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell responses for the GVL effect the kinetics of NK-cell reconstitution and differences in NK-cell repertoire using the different T-cell depletion protocols
Design
Single center prospective randomised phase III study
Population
Patients eligible for allogeneic SCT according to the standard criteria of our institution who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an HLA-identical sibling donor or an HLA-identical unrelated voluntary VUD donor
Intervention
T-cell depletion will be conducted using two different techniques either immunomagnetic CD34 selection or immunomagnetic CD3CD19 depletion
Endpoints
Primary endpoints are immunological reconstitution relapse disease free survival and overall survival Secondary endpoints NK-cell reconstitution and NK-cell mediated anti-tumour reactivity Cytotoxic T-cell responses for the GVL effect
Estimated efforts and risks for participating patients
We dont expect any extra patient efforts or risks because T-cell depletion is a standard procedure in our clinic for many years There is extensive experience with immunological T-cell depletion techniques We hypothesize CD3CD19 depletion will favour stem cell transplant outcome Immunological and molecular biological studies will be performed on blood samples already obtained as part of the standard protocol
Background
Removal of T-cells from the donor graft T-cell depletion offers the possibility for prevention of GVHD and subsequently less transplant related morbidity and mortality after allogeneic stem cell transplantation SCT There are several techniques to deplete T-cells from the stem cell grafts eg physical immunological and combined physical immunological separation methods All these techniques result in a stem cell graft with sufficient CD34 stem cells combined with an adequate depletion of T and B cells CD34 selected stem cell grafts are very pure and do not contain any additional cell populations In contrast CD3CD19 depleted grafts still contain NK-cells monocytes and dendritic cells that are part of the innate immune system Theoreticallythe presence of these cells may positively influence immunological reconstitution and the graft-versus-leukaemia GVL effect respectively resulting in improved outcome after SCT
Objectives
To evaluate the differences in immunological reconstitution transplant related mortality disease-free survival and overall survival after T-cell depleted allogeneic SCT for haematological malignancies using either immunomagnetic CD34 selection or immunomagnetic CD3CD19 depletion using the CliniMACS system in approximately 270 consecutive patients
Additionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution and differences in NK-cell repertoire will be monitored NK-cell mediated anti-tumor reactivity will be monitored in patients transplanted with and without NK-cells in the stem cell graft CD3CD19 depletion versus CD34 selection Secondary objectives are to evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell responses for the GVL effect the kinetics of NK-cell reconstitution and differences in NK-cell repertoire using the different T-cell depletion protocols
Design
Single center prospective randomised phase III study
Population
Patients eligible for allogeneic SCT according to the standard criteria of our institution who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an HLA-identical sibling donor or an HLA-identical unrelated voluntary VUD donor
Intervention
T-cell depletion will be conducted using two different techniques either immunomagnetic CD34 selection or immunomagnetic CD3CD19 depletion
Endpoints
Primary endpoints are immunological reconstitution relapse disease free survival and overall survival Secondary endpoints NK-cell reconstitution and NK-cell mediated anti-tumour reactivity Cytotoxic T-cell responses for the GVL effect
Estimated efforts and risks for participating patients
We dont expect any extra patient efforts or risks because T-cell depletion is a standard procedure in our clinic for many years There is extensive experience with immunological T-cell depletion techniques We hypothesize CD3CD19 depletion will favour stem cell transplant outcome Immunological and molecular biological studies will be performed on blood samples already obtained as part of the standard protocol
Detailed Description:
None
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