Inducing Graft Tolerance in HLA Haplotype Matched Related and 3 Ag Matched Unrelated Living Donor Kidney Transplantation (CIRM)
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03292445|
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : March 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Immune Tolerance||Procedure: Immune tolerance after kidney transplant Drug: Donor blood stem cells and T cells||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in HLA Haplotype Matched Related and 3 Ag HLA Matched Unrelated Living Donor Kidney Transplantation|
|Masking:||None (Open Label)|
|Official Title:||Induction of Immune Tolerance by Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in HLA Haplotype Matched Related and 3 Antigen HLA Matched Unrelated Living Donor Kidney Transplantation|
|Actual Study Start Date :||February 14, 2017|
|Estimated Primary Completion Date :||February 14, 2022|
|Estimated Study Completion Date :||February 14, 2024|
Experimental: Immune tolerance after kidney transplant
Immune tolerance after kidney transplant will be induced by transfusion of enriched donor blood stem cells and T cells to initiate blood cell mixed chimerism in patients conditioned with total lymphoid irradiation and rabbit anti-thymocyte globulin after kidney transplant. Patients will receive corticosteroids for 14 weeks with gradual dose reduction. They will also receive 12 months of mycophenolate mofetil and 18 months of tacrolimus with dose tapering beginning 9 months post-transplant and continuing as long as mixed chimerism is maintained and there is no evidence of graft versus host disease and no kidney rejection evident. Patients losing chimerism will continue on low dose immunosuppressive drug doses unless additional kidney rejection therapy is needed.
Procedure: Immune tolerance after kidney transplant
Induction of immune tolerance after kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and anti-thymocyte globulin followed by immunosuppressive drugs for 18 months. Immunosuppressive drugs are stopped if stable chimerism is achieved and there is no kidney rejection.
Drug: Donor blood stem cells and T cells
Immune tolerance after kidney transplantation resulting from mixed blood cells chimerism will be induced by donor blood stem cells and T cells given to the kidney recipient. Donor cells will be collected by apheresis after "mobilization" of blood stem cells from bone marrow 6-8 weeks before kidney transplant. Collected cells will undergo CD34 selection to recover >10 million donor blood stem cells/kg of patient weight to be combined with up to 150 million donor T cells/kg for transfusion soon after kidney transplant. The IND for this study covers the infusion of donor blood stem cells.
Other Name: Immune tolerance after kidney transplant
- Reduction of dependence on immunosuppressive drugs to prevent graft rejection. [ Time Frame: 24 months post-transplant ]Percentage of patients able to maintain normal renal function after coming off all immunosuppressive drug therapy and percentage of patients maintaining normal renal function with only minimum effective dose immunosuppressive drug monotherapy.
- Incidence of rejection episodes requiring corticosteroid therapy [ Time Frame: 24 months post-transplant ]Percentage of patients experiencing biopsy proven rejection episodes requiring corticosteroid therapy.
- Incidence of graft loss. [ Time Frame: 24 months post-transplant ]Percentage of patients experiencing loss of transplanted kidneys.
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): NCT03292445
|Contact: Asha Shori, CCRPemail@example.com|
|Contact: Stephan Busque, MD,MSfirstname.lastname@example.org|
|United States, California|
|Stanford University Medical Center||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Asha Shori, CCRP 650-736-0245 email@example.com|
|Contact: Stephan Busque, MD, MS 650-498-6189 firstname.lastname@example.org|
|Principal Investigator: John D Sandling, MD|
|Sub-Investigator: Judith A Shizuru, MD|
|Sub-Investigator: Marc L Melcher, MD|
|Sub-Investigator: Richard T Hoppe, MD|
|Sub-Investigator: Robert Lowsky, MD|
|Principal Investigator: Samuel Strober, MD|
|Principal Investigator: Stephan Busque, MD|
|Study Chair:||Samuel Md Strober, MD||Stanford University|