Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Treatment of Children With Kidney Transplants by Injection of CD4+CD25+FoxP3+ T Cells to Prevent Organ Rejection

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by The Russian State Medical University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Russian Academy of Medical Sciences
Information provided by (Responsible Party):
The Russian State Medical University
ClinicalTrials.gov Identifier:
NCT01446484
First received: October 3, 2011
Last updated: November 17, 2011
Last verified: November 2011

October 3, 2011
November 17, 2011
October 2011
November 2014   (final data collection date for primary outcome measure)
Patient and graft survival [ Time Frame: At 1 years post-transplant ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01446484 on ClinicalTrials.gov Archive Site
  • Patient and graft survival [ Time Frame: At 3 years post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence rate of biopsy-proven acute rejection, defined as a renal biopsy demonstrating acute cellular or humoral rejection of Banff Grade IA or greater [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24-hour urine protein excretion [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events associated with renal transplantation and immunosuppression [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Treatment of Children With Kidney Transplants by Injection of CD4+CD25+FoxP3+ T Cells to Prevent Organ Rejection
Phase 1 Pilot Study Using Autologous CD4+CD25+FoxP3+ T Regulatory Cells and Campath-1H to Induce Renal Transplant Tolerance

T regulatory cells (T regs) are responsible for immune tolerance in solid organ transplant patients. This study will evaluate the treatment of children with kidney transplants either with Campath and other immune system suppressing medications alone or in combination with injection of autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells expanded ex vivo. The aim of this study is to develop a new strategy that will be more effective in preventing organ rejection and maintaining patient health.

Kidney transplantation is a common procedure in hospitals, but organ rejection and serious side effects are potential problems for patients. Alemtuzumab is a monoclonal antibody to CD52 that binds to and depletes excess of T cells in the bone marrow of leukemia patients. In this study alemtuzumab will be used to deplete the recipient's white blood cells (WBCs) at the time of transplantation.

An experimental group of patients will receive two injections of autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells expanded ex vivo at day 30 and day 180 after transplantation. T regulatory cells are responsible for immune system tolerance induction. Treatment with these cells is believed to create tolerance when T cell immune responses to transplant alloantigens are decreased. This study will evaluate the safety and effectiveness of an antirejection regimen including alemtuzumab and other immunosuppressive medications combined with autologous T regs injections in patients undergoing kidney transplantation (Tx). Patients will receive i.v. injection of alemtuzumab on Days 14-21 before Tx and on Day 0. Starting on Day 0, patients will begin taking either tacrolimus or cyclosporine, and on Day 2-3 - mycophenolate mofetil.

This study will continue during three years. Participants will be randomly assigned to receive either the full immunosuppressive therapy and autologous T regs by s.c. injection (group 1) or immunosuppressive therapy alone (group 2). Prior to immunosuppressive therapy in the group 1, blood samples will be collected twice with at least one-week interval between collections in the amount of 70 ml/1,73 m2 . Two ml of blood will be collected before starting of immunosuppressive therapy and levels of T regs in periphery blood will be examined by flow cytometry analysis in both groups. T cells CD4+ will be separated from these blood samples and will be frozen in liquid nitrogen.

All patients will undergo kidney transplantation. One month after transplantation the flow cytometry analysis of blood samples will be performed in both groups. The patients in group 1 will undergo by subcutaneous injection of approximately 2x10^8 autologous T regs expanded from previously frozen CD4+ cells in a month and 180 days after transplantation. One week following the injection, an additional flow cytometry analysis will be performed to evaluate T reg levels in patient's blood.

The level of T regs in patient's blood will be repeated in both groups after 90-120 days following transplantation.

Patients will be monitored during three years post-transplantation. Urine samples will be collected after one week and 1, 3, 6, and 9 months following transplantation. Kidney biopsy will be performed at Months 1, 12, and 36. Based on results of biopsy analysis, kidney function and signs of over-immunosuppression, some patients will be switched from CNIs (calcineurin inhibitors, tacrolimus or cyclosporine) to PSIs regiment (sirolimus or everolimus).

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • End-Stage Renal Disease
  • Kidney Failure
  • Biological: CD4+CD25+CD127lowFoxP3+ T regulatory cells injection
    Blood samples from patients in the experimental group will be collected twice with weekly interval in the amount of 70 ml/1,73 m2. T cells CD4+ will be separated from blood samples and frozen in liquid nitrogen. At day 30 after transplantation patients will undergo subcutaneous injection of approximately 2x 10^8 autologous T regs, expanded from previously frozen CD4+ T cells. Levels of T reg cells in patient's blood will be estimated by flow cytometry in a week after injection. That cell injection procedure will be repeated at 6 months after transplantation
    Other Name: Cell therapy
  • Drug: Alemtuzumab
    Immunosuppressant; 2 doses of drug by intravenous infusion on Days 14 - 21 before Tx and on Day 0 after Tx
    Other Name: Campath
  • Drug: Mycophenolate mofetil
    Immunosuppressant; oral daily dose starting Day 2-3 until withdrawal or end of the study
    Other Name: Cellcept
  • Drug: Sirolimus
    Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study
    Other Names:
    • Rapamycin
    • Rapamune
  • Drug: Tacrolimus
    Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study
    Other Name: Prograf
  • Drug: Cyclosporine
    Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study
    Other Name: Neoral
  • Drug: Everolimus
    Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study
    Other Names:
    • Certican
    • Afinitor
  • Procedure: Kidney transplantation
    Living related kidney transplantation
    Other Name: Renal Transplantation
  • Experimental: T reg therapy
    Kidney transplantation, followed by immunotherapy given along with autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells infusions
    Interventions:
    • Biological: CD4+CD25+CD127lowFoxP3+ T regulatory cells injection
    • Drug: Alemtuzumab
    • Drug: Mycophenolate mofetil
    • Drug: Sirolimus
    • Drug: Tacrolimus
    • Drug: Cyclosporine
    • Drug: Everolimus
    • Procedure: Kidney transplantation
  • Active Comparator: Immunosuppression
    Patients will undergo immunosuppressive therapy followed by living related kidney transplantation
    Interventions:
    • Drug: Alemtuzumab
    • Drug: Mycophenolate mofetil
    • Drug: Sirolimus
    • Drug: Tacrolimus
    • Drug: Cyclosporine
    • Drug: Everolimus
    • Procedure: Kidney transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
November 2014
November 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Weight greater than 10 kg ( lbs)
  • Will be receiving a living-related primary kidney allograft
  • Negative B-cell and T-cell cytotoxic and flow cytometry crossmatch
  • Normal echocardiogram (ECG) with an ejection fraction of greater than 50%
  • Received full course of vaccination for hepatitis B virus (HBV), completed at least 6 weeks before transplantation, OR has naturally acquired immunity
  • Parents willing to comply with the study visits

Exclusion Criteria:

  • Previously received or is receiving an organ transplant other than a kidney
  • Receiving an ABO incompatible donor kidney
  • HIV infected
  • Antibody positive for hepatitis C virus
  • Surface antigen positive for HBV
  • Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB (positive Mantoux test)
  • Current cancer or a history of cancer within the 5 years prior to study entry. Patients who have had successfully treated nonmetastatic basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix are not excluded.
  • Significant liver disease, defined as having continuously elevated AST (SGOT) or ALT (SGPT) levels greater than 3 times the upper value of the normal range within 28 days prior to study entry
  • Uncontrolled concomitant infections, severe diarrhea, vomiting, active upper gastrointestinal tract malabsorption, active peptic ulcer, or any other unstable medical condition that could interfere with this study
  • Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant
  • Currently receiving any immunosuppressive agent
  • Anticipated contraindication to taking medications orally or via nasogastric tube by the morning of Day 2 following completion of the transplant procedure
  • Require certain medications
  • Known hypersensitivity to any of the study medications,
  • Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study
  • Anticipated contraindication to study medications administration for longer than 5 days post-transplant
Both
1 Year to 18 Years
No
Contact: Svetlana N. Bykovskaia, M.D. Ph.D. 7-916-4362291 sbykovskaia@gmail.com
Contact: Anton A. Keskinov, Ph.D. 7-495-4341444 a.keskinov@mail.ru
Russian Federation
 
NCT01446484
RSMU-001
No
The Russian State Medical University
The Russian State Medical University
Russian Academy of Medical Sciences
Principal Investigator: Svetlana N. Bykovskaia, M.D. Ph.D. Russian State Medical University
Principal Investigator: Michael M. Kaabak, M.D. Ph.D. Boris Petrovsky's Scientific Center of Surgery Russian Academy of Medical Sciencies
The Russian State Medical University
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP