Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00186823
Status:
COMPLETED
Last Update Posted:
2009-01-29
First Post:
2005-09-09
Brief Title:
Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Haploidentical Stem Cell Transplantation Utilizing Purified CD34 Hematopoietic Cells for Patients With Hematologic Malignancies
Status:
COMPLETED
Status Verified Date:
2009-01
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:
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies However most patients do not have an appropriate HLA immune type matched sibling donor available andor are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner Another option is haploidentical transplant using a partially matched family member donor
Although haploidentical transplant has proven curative in many patients this procedure has been hindered by significant complications primarily regimen-related toxicity including graft versus host disease GVHD and infection due to delayed immune reconstitution These can in part be due to certain white blood cells in the graft called T cells GVHD happens when the donor T cells recognize the body tissues of the patient the host are different and attack these cells Although too many T cells increase the possibility of GVHD too few may cause the recipients immune system to reconstitute slowly or the graft to fail to grow leaving the patient at high-risk for significant infection
This research project will investigate the use of particular pre-transplant conditioning regimen chemotherapy antibodies and total body irradiation followed by a stem cell infusion from a mismatched family member donor Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor
Although haploidentical transplant has proven curative in many patients this procedure has been hindered by significant complications primarily regimen-related toxicity including graft versus host disease GVHD and infection due to delayed immune reconstitution These can in part be due to certain white blood cells in the graft called T cells GVHD happens when the donor T cells recognize the body tissues of the patient the host are different and attack these cells Although too many T cells increase the possibility of GVHD too few may cause the recipients immune system to reconstitute slowly or the graft to fail to grow leaving the patient at high-risk for significant infection
This research project will investigate the use of particular pre-transplant conditioning regimen chemotherapy antibodies and total body irradiation followed by a stem cell infusion from a mismatched family member donor Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor
Detailed Description:
Secondary outcome evaluations for this clinical study include the following
To estimate overall survival disease free survival and event free survival for these patients
To estimate the incidence of grade 2 to 4 acute GvHD in these patients
To estimate the incidence of chronic GvHD and graft failure in these patients
To estimate the incidence of non-hematologic peri-transplant regimen-related toxicity and regimen-related mortality in the first 100 days after transplantation in these patients
To estimate the number of patients who require donor lymphocyte infusions andor stem cell boosts after transplantation in this group of patients and evaluate its impact on immune reconstitution and engraftment
To estimate the number of patients who develop evidence of EBV reactivation or post transplant lymphoproliferative disease PTLPD post transplant in this group of patients
Describe the pharmacokinetics of rabbit anti-thymocyte globulin rATG in patients receiving allogeneic transplantation and determine the frequency of rATG antibody development
Explore dose and patient characteristics as determinants of active rATG pharmacokinetic parameters
Originally this study began as a randomized comparison of two methods of stem cell selection utilizing the CliniMACS device Both arms provided a purified product of CD34 hematopoietic cells that was depleted of T-lymphocytes One arm utilized a positive selection methodology using an anti-CD34 antibody and the other arm utilized negative selection with the anti-CD3 antibody OKT-3 There were no toxicities noted that would have required the study to be interrupted early however due to low accrual it was decided to redesign the study The new design focused on the standard arm utilizing negative selection and all subsequent participants were treated in that manner The patients who were treated on the positive selection arm are continuing to be monitored as specified in the original protocol but will be reported in a descriptive manner only The primary and secondary objectives of the current version of this study will be answered only by those patients receiving a haploidentical stem cell transplant utilizing a negative selection methodology
To estimate overall survival disease free survival and event free survival for these patients
To estimate the incidence of grade 2 to 4 acute GvHD in these patients
To estimate the incidence of chronic GvHD and graft failure in these patients
To estimate the incidence of non-hematologic peri-transplant regimen-related toxicity and regimen-related mortality in the first 100 days after transplantation in these patients
To estimate the number of patients who require donor lymphocyte infusions andor stem cell boosts after transplantation in this group of patients and evaluate its impact on immune reconstitution and engraftment
To estimate the number of patients who develop evidence of EBV reactivation or post transplant lymphoproliferative disease PTLPD post transplant in this group of patients
Describe the pharmacokinetics of rabbit anti-thymocyte globulin rATG in patients receiving allogeneic transplantation and determine the frequency of rATG antibody development
Explore dose and patient characteristics as determinants of active rATG pharmacokinetic parameters
Originally this study began as a randomized comparison of two methods of stem cell selection utilizing the CliniMACS device Both arms provided a purified product of CD34 hematopoietic cells that was depleted of T-lymphocytes One arm utilized a positive selection methodology using an anti-CD34 antibody and the other arm utilized negative selection with the anti-CD3 antibody OKT-3 There were no toxicities noted that would have required the study to be interrupted early however due to low accrual it was decided to redesign the study The new design focused on the standard arm utilizing negative selection and all subsequent participants were treated in that manner The patients who were treated on the positive selection arm are continuing to be monitored as specified in the original protocol but will be reported in a descriptive manner only The primary and secondary objectives of the current version of this study will be answered only by those patients receiving a haploidentical stem cell transplant utilizing a negative selection methodology
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