Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mesenchymal Stem Cells Under Basiliximab/Low Dose RATG to Induce Renal Transplant Tolerance

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: NCT00752479
Recruitment Status : Terminated (Necessity of major revision of the protocol)
First Posted : September 15, 2008
Last Update Posted : April 9, 2015
Sponsor:
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief Summary:

This a pilot, explorative study to define the safety and biological/mechanistic effect of the systemic intravenous infusion of syngeneic ex-vivo expanded MSCs in living-related kidney transplant recipients (one or two HLA haplotype mismatches) under basiliximab/low-dose RATG induction therapy and maintenance immunosuppressive drugs with the ultimate objective to test the feasibility of safely achieving graft tolerance in a subsequent efficacy pilot study.

Specific objectives To compare changes in the immunophenotype and ex-vivo T-cell functional tests from samples of peripheral blood and measurement in the urine of messenger RNA for FoxP3,in kidney transplant recipients given or not syngeneic (from the recipient) MSC infusion under basiliximab/low-dose RATG induction therapy and maintenance immunosuppressive treatment with low-dose cyclosporine (CsA) plus low-dose mycophenolate mofetil (MMF).

This will assess at different time up to 12 months post transplant. In addition the safety profile of MSC infusion will be investigated. We have planned to start with the safety and biological/mechanistic study in 6 living-related kidney transplant recipients. Three patients will receive ex-vivo expanded syngeneic MSC infusion (2x106 MSCs per kilogram body weight) at the time of kidney transplant, and 3 additional patients no cells (controls), both under the cover of induction therapy with basiliximab and low-dose RATG, and maintenance immunosuppression with low-dose CsA and MMF. Randomization to MSC or no cell infusion will be performed at the time the recipient will sign the informed consent to participate to the study.

Should this biological/mechanistic ex vivo studies document that MSC infusion allows the development of an immune microenvironment permissive to graft tolerance, a pilot efficacy study to achieve operational tolerance after complete withdrawal of maintenance immunosuppressive therapy will follow.

In this additional pilot explorative efficacy study all consecutive patients will be included and followed until the first episode of rejection (if any) will occur or 29 consecutive patients have successfully withdrawn the immunosuppressive therapy. This has been estimated according to the Simon's two-stage minimax design.


Condition or disease Intervention/treatment Phase
Kidney Transplant Biological: Mesenchymal stem cells infusion, Basiliximab,Methylprednisolone,RATG ,Cyclosporine ,Mycophenolate mofetil Drug: Basiliximab, Methylprednisolone,RATG,Cyclosporine,Mycophenolate mofetil Phase 1 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Mesenchymal Stem Cells Under Basiliximab/Low Dose RATG to Induce Renal Transplant Tolerance
Study Start Date : May 2008
Actual Primary Completion Date : July 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1 Biological: Mesenchymal stem cells infusion, Basiliximab,Methylprednisolone,RATG ,Cyclosporine ,Mycophenolate mofetil

Cell therapy

Mesenchymal cells infusion.

Induction therapy:

Basiliximab (20 mg i.v.day 0 and day 4 post-tx). Low dose RATG (0.5 mg/kg/day i.v. day 0-6 post-tx). Methylprednisolone (500 mg to 25 mg from day 0 to 6 post-tx. Then stop).

Maintenance therapy:

Cyclosporine (from day 0: dose according to target trough blood level). Mycophenolate mofetil (750 mg b.i.d. from day 1 post-tx).


Active Comparator: 2 Drug: Basiliximab, Methylprednisolone,RATG,Cyclosporine,Mycophenolate mofetil

Routine immunosuppressive therapy

Induction therapy:

Basiliximab (20 mg i.v.day 0 and day 4 post-tx). Low dose RATG (0.5 mg/kg/day i.v. day 0-6 post-tx). Methylprednisolone (500 mg to 25 mg from day 0 to 6 post-tx. Then stop).

Maintenance therapy:

Cyclosporine (from day 0: dose according to target trough blood level). Mycophenolate mofetil (750 mg b.i.d. from day 1 post-tx).





Primary Outcome Measures :
  1. Assessing the percentage of inhibition of memory T cell response and/or naive T cell response, the induction of donor-reactive T cell anergy and the appearance in the peripheral blood of regulatory T cells. [ Time Frame: at 12 months post-kidney transplant ]

Secondary Outcome Measures :
  1. Safety parameters related to MSC infusion, graft function, graft rejection [ Time Frame: at 12 months post-kidney transplant ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients
  • Aged 18 or older
  • Non-HLA identical with the donor (one or two haplotype mismatches)
  • First kidney transplant
  • Capable of understanding the purpose and risk of the study
  • Written informed consent

Exclusion Criteria:

  • MSC donor positive for HIV-1, HIV-2, HBV, HCV, Syphilis.
  • Specific contraindication to MSC infusion
  • Any clinical relevant condition that might affect study participation and/or study results
  • Pregnant women and nursing mothers
  • Unwillingness or inability to follow study protocol in the investigator's opinion

Information from the National Library of Medicine

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): NCT00752479


Locations
Layout table for location information
Italy
Nephrology Unit
Bergamo, BG, Italy, 24128
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Investigators
Layout table for investigator information
Study Chair: Giuseppe Remuzzi, MD Department of Immunology and Clinical Transplantation / Mario Negri Institute for Pharmacological Research and Ospedali Riuniti BG
Principal Investigator: Norberto Perico, MD Mario Negri Institute for Pharmacological Research, Ranica BG
Principal Investigator: Marina Noris, CH Ph Mario Negri Institute for Pharmacological Research, Ranica BG
Principal Investigator: Martino Introna, MD Cell and Gene therapy Laboratory "G. Lanzani" BG
Principal Investigator: Alessandro Rambaldi, MD Hematology Unit - Ospedali Riuniti BG

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT00752479     History of Changes
Other Study ID Numbers: MSC TX
2009−012350−20 ( EudraCT Number )
First Posted: September 15, 2008    Key Record Dates
Last Update Posted: April 9, 2015
Last Verified: April 2015
Keywords provided by Mario Negri Institute for Pharmacological Research:
living
related
Additional relevant MeSH terms:
Layout table for MeSH terms
Cyclosporine
Mycophenolic Acid
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Cyclosporins
Basiliximab
Thymoglobulin
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents