Ignite Creation Date:
2024-05-06 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 12:49 PM
Study NCT ID:
NCT03591302
Status:
RECRUITING
Last Update Posted:
2022-05-10
First Post:
2018-06-18
Brief Title:
Delayed Blood Stem Transplantation in HLA Matched Kidney Transplant Recipients to Eliminate Immunosuppressive Drugs
Sponsor:
Stephan Busque
Organization:
Stanford University
Study Overview
Official Title:
Total Lymphoid Irradiation Anti-Thymocyte Globulin and Purified Donor CD34 and T-cell Transfusion to Withdraw Immunosuppressive Drugs From Recipients of a Previous HLA Matched Living Donor Kidney Transplantation
Status:
RECRUITING
Status Verified Date:
2022-05
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:
The study will determine whether patients with functioning Human Leukocyte Antigen HLA matched kidney transplants for at least one year and who want to discontinue immunosuppressive drugs can be treated with Total Lymphoid Irradiation TLI and rabbit Anti-Thymocyte Globulin rATG and an HLA matched donor hematopoietic progenitor cell infusion such that their drugs are successfully withdrawn while maintaining normal renal function
Detailed Description:
This is a single-center open-label study in adult renal transplant patientsTwenty five patients with functioning HLA matched living donor kidney transplants will receive TLI rATG and an infusion of cluster of differentiation CD34 StemProgenitor cells selected granulocyte colony-stimulating factor G-CSF mobilized blood cells combined with CD3 T cells Stem Progenitor cells from their transplant donorsTransplant recipients will have their maintenance Immunosuppressive drugs adjusted for four weeks before starting the TLI and ATG conditioning regimen Mycophenolate Mofetil MMF will be maintained at 05 gm twice a day per day during this four week period during TLI and ATG treatments and increased to 1 gram twice a day immediately after the completion of TLI at day 14
MMF will be tapered starting 6 six months later Tacrolimus levels will be targeted to blood trough levels of 4-6 ngml in the month before the start of the conditioning regimen This target would be increased to 8-10 ngml at the start of the TLI and ATG conditioning regimen At serial time points 1 graft function will be monitored 2 chimerism will be measured in recipient white blood cell subsets 3 protocol biopsies of the graft will be obtained An attempt will be made to discontinue Tacrolimus at 12 months if 1 chimerism is detectable for least 180 days after the CD34 and CD3 cell infusion 2 there is no Graft Versus Host Disease GVHD 3 there is stable graft function without clinical rejection episodes and 4 lack of histological rejection on protocol biopsies
Recipients will be given the target dose of 8 x 106 CD 34 cellsKg and a dose of 5x106 CD3 cellsKgThe dose would be sequentially increased to 10 15 and 25 x 106 CD3 cellsKg if fewer than 4 of 5 consecutive patients achieve whole blood chimerism of 30 at 60 days If 4 of 5 patients achieve this level of chimerism then all subsequent enrolled patients will receive this dose
MMF will be tapered starting 6 six months later Tacrolimus levels will be targeted to blood trough levels of 4-6 ngml in the month before the start of the conditioning regimen This target would be increased to 8-10 ngml at the start of the TLI and ATG conditioning regimen At serial time points 1 graft function will be monitored 2 chimerism will be measured in recipient white blood cell subsets 3 protocol biopsies of the graft will be obtained An attempt will be made to discontinue Tacrolimus at 12 months if 1 chimerism is detectable for least 180 days after the CD34 and CD3 cell infusion 2 there is no Graft Versus Host Disease GVHD 3 there is stable graft function without clinical rejection episodes and 4 lack of histological rejection on protocol biopsies
Recipients will be given the target dose of 8 x 106 CD 34 cellsKg and a dose of 5x106 CD3 cellsKgThe dose would be sequentially increased to 10 15 and 25 x 106 CD3 cellsKg if fewer than 4 of 5 consecutive patients achieve whole blood chimerism of 30 at 60 days If 4 of 5 patients achieve this level of chimerism then all subsequent enrolled patients will receive this dose
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None