Induction of Donor Specific Tolerance in Recipients of Live Donor Kidney Allografts by Donor Stem Cell Infusion
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00498160|
Recruitment Status : Active, not recruiting
First Posted : July 9, 2007
Last Update Posted : December 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Renal Failure||Biological: Enriched Hematopoetic Stem Cell Infusion||Phase 1 Phase 2|
Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial. More info ...
At the present time, kidney transplant recipients must take anti-rejection medication to prevent rejection of the donated kidney. Even with this medication, chronic rejection is the most common cause of late graft loss. The anti-rejection agents themselves are significantly toxic, with side effects including kidney damage, infection and an increased incidence of cancer. The goal of this study is to allow the patient to develop "tolerance" to the transplanted kidney while maintaining a competent immune system. Tolerance enables the transplant recipient's body to recognize the transplanted organ as self rather than foreign tissue. The recipient will not try to reject the donor kidney and the need for anti-rejection medication could be dramatically decreased or eliminated entirely. To accomplish this, patients in this study will receive specially treated bone marrow taken from their kidney donor. Bone marrow transplant has been shown in animal studies and in humans to induce tolerance following organ transplant.
Two factors limit the application of donor marrow transplant to induce tolerance: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully, a state called mixed chimerism. The toxicity of conditioning and transplantation is significantly reduced.
In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in living donor or deceased donor kidney transplant recipients. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. We believe this study will provide a breakthrough in the approach to kidney transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following kidney transplant and reduce or eliminate the need for anti-rejection therapy.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||1) Induction of Donor Specific Tolerance in Recipients of Kidney Allografts by Donor Bone Marrow Cell Infusion (Deceased Donors) and 2) Induction of Donor Specific Tolerance in Recipients of Live Donor Kidney Allografts by Donor Stem Cell Infusion|
|Study Start Date :||January 2005|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||December 2024|
Experimental: Living or Deceased Donor Kidney Allograft
Recipients with the need for a living kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same living donor. Recipients with the need for a deceased donor kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same deceased donor
Biological: Enriched Hematopoetic Stem Cell Infusion
Enriched Hematopoetic Stem Cell Infusion
- Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment [ Time Frame: one month to three years ]Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
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): NCT00498160
|United States, Illinois|
|Northwestern Memorial Hospital|
|Chicago, Illinois, United States, 60611|
|United States, Kentucky|
|University of Louisville|
|Louisville, Kentucky, United States, 40202|
|OverallOfficial:||Suzanne T Ildstad, MD||University of Louisville|