Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance (ASCOTT)
|Complication of Transplanted Organ, Nos||Other: Autologous Hematopoietic Stem Cell Transplant||Phase 2 Phase 3|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance|
- Number of patients who develop tolerance post autologous HSCT [ Time Frame: 24 months post HSCT ]Number of patients who develop tolerance at 24 months post HSCT as defined clinically and histologically in the absence of any immunosuppression in liver transplant recipients.
- HSCT mortality [ Time Frame: 2 years post HSCT ]
- HSCT related morbidity [ Time Frame: at 2 years post HSCT ]
- Rate of immune reconstitution [ Time Frame: at 2 years post HSCT ]
|Study Start Date:||December 2015|
|Estimated Study Completion Date:||January 2020|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Experimental: Autologous HSCT
Eligible participants will undergo an Autologous Hematopoietic Stem Cell Transplant (HSCT) as a two-step intervention.
Other: Autologous Hematopoietic Stem Cell Transplant
Step 1: Participants will receive intravenous chemotherapy and cytokine-based treatment for mobilization of hematopoietic stem cells (HSC) into the circulation, followed by collection using peripheral vein leukopheresis. The HSC graft product will undergo ex vivo purification with CD34 selection using Miltenyil CliniMACS and cryopreserved.
Step 2: Intravenous busulphan, cyclophosphamide and anti-thymocyte globulin will be administered to participants to achieve immune ablation prior to the infusion of the participants' own thawed HSC graft product (HSC transplant). Routine supportive measures will be employed during the recovery from the chemotherapy and HSCT. Participants' immune suppression will be stopped at the time of immunoablative therapy and will be switched to everolimus which will be discontinued at 6 months post HSCT.
Other Name: HSCT
Although short-term results for liver transplantation are excellent, the need for immunosuppression limits quality of life and long-term survival.
Investigators plan to examine the utility and safety of autologous hematopoietic stem cell transplantation (HSCT) to allow withdrawal of immunosuppression in 10 liver transplant recipients who are at a high risk of developing recurrent liver damage from repeated bouts of rejection, or recurrent disease or who have a high likelihood of developing serious medical complications from complications of immune suppression.
Hematopoietic stem cells will be mobilized, purified and cryopreserved. Following a chemotherapy and Anti-thymocyte Globulin (ATG) based-regimen for immune ablation, the purified stem cells will be thawed and infused back into participants (autologous hematopoietic stem cell transplant - HSCT). Participants will be converted to everolimus, a mammalian target of rapamycin inhibitor (mTORi), which will be continued for 6 months and then withdrawn based on histologic evidence of graft acceptance.
Participants will be followed closely for a total of 24 months for any biochemical and histologic evidence of tolerance or rejection. Re-vaccination to common viral and bacterial antigens will be undertaken as required using a standard protocol for recipients of a hematopoietic stem cell transplant (HSCT).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02549586
|The Ottawa Hopital|
|Ottawa, Ontario, Canada, K1H 8L6|
|Multi-Organ Transplant Program, Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2N2|
|Principal Investigator:||Gary A Levy, MD FRCP AGAF||University of Toronto Transplant Institute - Multi Organ Transplant Program|
|Principal Investigator:||Harold L Atkins, MD FRCP(C)||Ottawa Hospital Research Institute|