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Trial record 1 of 1 for:    NCT02549586
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Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance (ASCOTT)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Ottawa Hospital Research Institute
Information provided by (Responsible Party):
Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto
ClinicalTrials.gov Identifier:
NCT02549586
First received: September 1, 2015
Last updated: October 27, 2016
Last verified: October 2016
  Purpose
This open-label, proof-of-principle two center cohort study will evaluate the ability of autologous hematopoietic stem cell transplantation to induce tolerance in recipients of deceased or live donor liver transplants (ASCOTT). A maximum of 10 participants will be entered at a minimum of 3 months post liver transplant. The participants will undergo autologous hematopoietic stem cell transplants (HSCT) to "re-educate" their immune systems to accept the graft without the need for long term immunosuppression (tolerance).

Condition Intervention Phase
Complication of Transplanted Organ, Nos Other: Autologous Hematopoietic Stem Cell Transplant Phase 2 Phase 3

Study Type: Interventional
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

Further study details as provided by Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 10
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)
Arms Assigned Interventions
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

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants must be 18 years of age or older.
  2. Participants must be a minimum of 6 months post-transplant;
  3. Participants are recipients of a hepatic allograft for alcohol induced liver disease; or a genetic form of liver disease such as hemochromatosis or Wilson's disease; or an autoimmune liver disease including sclerosing cholangitis, autoimmune hepatitis, and/or primary biliary cirrhosis.
  4. Participants have a complication of transplantation that might be ameliorated by HSCT and/or withdrawal of immunosuppression such as: evidence of recurrent autoimmune disease in the graft; repeated episodes (minimum of 2) of acute cellular rejection; and/ or development of adverse events related to immune suppression which have not been well managed by conventional methods including drug dose reduction or substitution of other medications. Examples include progression of renal dysfunction, repeated infections, neurologic complications, cardiovascular complications, or post-transplant lymphoproliferative disease (PTLD) that has been in remission for at least 12 months. These complications must be deemed serious enough to warrant inclusion in the study by the investigator.

Exclusion Criteria:

  1. Participants < 18 yr.
  2. Participants with cardiac, renal, pulmonary, hepatic, or other organ impairment that would limit their ability to receive dose intensive chemotherapy;
  3. Participants with any active or chronic infection. Participants with previous reactivation of Epstein-Barr virus, cytomegalovirus , BK, human herpesvirus 6 or varicella-zoster virus would be considered eligible if the virus has returned to a latent state;
  4. Participants who are seropositive for HIV1, HIV2, Hepatitis B Surface Antigen, and Hepatitis C;
  5. Participants with a previous history of a malignancy other than squamous or basal cell carcinoma of the skin, or post-transplant lymphoproliferative disease (PTLD);
  6. Participants whose life expectancy is severely limited by another co-morbid illness;
  7. Participants with evidence of myelodysplasia, other non-autoimmune cytopenia, or an inherited immunodeficiency state;
  8. Pregnancy or Participants who are unwilling to practice two active forms of contraception during the time of chemotherapy administration. Participants must be willing to commit to not becoming pregnant from enrollment in the study until 2 years following their HSCT.
  9. Participants unable to comply with the medical treatment specified in the protocol;
  10. Participants unable to give written informed consent in accordance with research ethics board guidelines.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02549586

Locations
Canada, Ontario
The Ottawa Hopital
Ottawa, Ontario, Canada, K1H 8L6
Multi-Organ Transplant Program, Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
Gary A Levy, O. Ont. MD. FRCP AGAF
Ottawa Hospital Research Institute
Investigators
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
  More Information

Publications:

Responsible Party: Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto
ClinicalTrials.gov Identifier: NCT02549586     History of Changes
Other Study ID Numbers: Tol 001
Study First Received: September 1, 2015
Last Updated: October 27, 2016

Keywords provided by Gary A Levy, O. Ont. MD. FRCP AGAF, University of Toronto:
solid organ transplant
immune tolerance
autologous stem cell transplant
blood and marrow transplant
autoimmune disease

ClinicalTrials.gov processed this record on June 23, 2017