Delayed Blood Stem Transplantation in HLA Matched Kidney Transplant Recipients to Eliminate Immunosuppressive Drugs.
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|ClinicalTrials.gov Identifier: NCT03591302|
Recruitment Status : Not yet recruiting
First Posted : July 19, 2018
Last Update Posted : July 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Immune Tolerance||Biological: Hematopoietic cell transplantation Radiation: Total Lymphoid irradiation||Phase 1|
This is a single-center, open-label study in adult renal transplant patients.Twenty five patients with functioning HLA matched living donor kidney transplants will receive TLI, rATG and an infusion of cluster of differentiation (CD)34+ (Stem/Progenitor cells) selected granulocyte colony-stimulating factor (G-CSF) mobilized blood cells combined with CD3+ T cells (Stem/ Progenitor cells) from their transplant donors.Transplant 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 0.5 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 ng/ml in the month before the start of the conditioning regimen. This target would be increased to 8-10 ng/ml 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 10^6 CD 34 + cells/Kg and a dose of 5x10^6 CD3+ cells/Kg.The dose would be sequentially increased to 10, 15 and 25 x 10^6 CD3+ cells/Kg 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in previous HLA Matched Living Donor Kidney Transplantation|
|Masking:||None (Open Label)|
|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 .|
|Estimated Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||October 1, 2021|
|Estimated Study Completion Date :||October 1, 2025|
Experimental: Immune tolerance, Kidney transplantation
Intervention: HLA matched living donor recipients of a functioning kidney transplant graft at one year will receive hematopoietic cell transplantation and Total lymphoid irradiation. The intervention is intended to induce immune tolerance such as to allow withdrawal of the immunosuppressive drugs. Immune tolerance is achieved through the development of donor/recipient mixed chimerism following combined kidney and hematopoietic stem cell transplantation from the living donor.
Biological: Hematopoietic cell transplantation
Transplantation of hematopoietic stem cells from living donor.
Radiation: Total Lymphoid irradiation
Total lymphoid irradiation is used as part of the conditioning regimen for the hematopoietic stem cell transplant.
- Percentage of patients no longer dependent on immunosuppressive drugs to maintain normal renal function. [ Time Frame: six months to up to five years post stem cell transplant ]A patient will be considered no longer dependent if able to maintain normal renal function after coming off immunosuppressive medications.
- Percentage of patients experiencing biopsy proven rejection episodes requiring treatment requiring corticosteroids. [ Time Frame: One year to five years ]
- Percentage of patients experiencing graft loss. [ Time Frame: One year to five years ]
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): NCT03591302
|Contact: Asha Shori, CCRPemail@example.com|
|Contact: Stephan Busque, MD,MSfirstname.lastname@example.org|
|United States, California|
|Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|Study Chair:||Samuel Md Strober, MD||Stanford University|