End-Stage Renal DiseasePhase 1/2NCT01446484
Treatment of Children With Kidney Transplants by Injection of CD4+CD25+FoxP3+ T Cells to Prevent Organ Rejection
A Phase 1/2 study testing CD4+CD25+CD127lowFoxP3+ T regulatory cells injection, Alemtuzumab and Mycophenolate mofetil in people with End-Stage Renal Disease and Kidney Failure, run by Pirogov Russian National Research Medical University at 2 sites in Russia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- End-Stage Renal Disease, Kidney Failure
- What is being tested?
- CD4+CD25+CD127lowFoxP3+ T regulatory cells injection, Alemtuzumab and Mycophenolate mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesRussia
- Study dates
- Oct 2011to Nov 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Russia2 sites, 2 recruiting
- Recruiting
The Russian State Medical University
Moscow, 117997
Svetlana N. Bykovskaia, M.D. Ph.D., 7-916-4362291, sbykovskaia@gmail.com
Anton A. Keskinov, Ph.D., 7-495-4341444, a.keskinov@mail.ru
- Recruiting
Boris Petrovsky Scientific Center of Surgery Russian Academy of Medical Sciencies
Moscow, 119991
Michael M. Kaabak, M.D. Ph.D., 7-499-2481344, kaabak@pochka.org
Nadezhda Babenko, 7-499-2481344, babenko@pochka.org
About this study
Official title: 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.
Read the detailed description
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).
- Conditions
- End-Stage Renal Disease, Kidney Failure
- Being tested
- CD4+CD25+CD127lowFoxP3+ T regulatory cells injection, Alemtuzumab, Mycophenolate mofetil, Sirolimus, Tacrolimus
- Keywords
- Renal transplantation, Kidney transplantation, CD4+CD25+CD127lowFoxP3+ T Regulatory Cells, T reg, Campath
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4+CD25+CD127lowFoxP3+ T regulatory cells injectionBiological
Also called Cell therapy
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
AlemtuzumabDrug
Also called Campath
Immunosuppressant; 2 doses of drug by intravenous infusion on Days 14 - 21 before Tx and on Day 0 after Tx
Also called Cellcept
Immunosuppressant; oral daily dose starting Day 2-3 until withdrawal or end of the study
SirolimusDrug
Also called Rapamycin, Rapamune
Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study
TacrolimusDrug
Also called Prograf
Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study
CyclosporineDrug
Also called Neoral
Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study
EverolimusDrug
Also called Certican, Afinitor
Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study
Kidney transplantationProcedure or surgery
Also called Renal Transplantation
Living related kidney transplantation
| Study group | Role | What they receive |
|---|---|---|
| T reg therapy | Experimental | Kidney transplantation, followed by immunotherapy given along with autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells infusions Receives: Biological: CD4+CD25+CD127lowFoxP3+ T regulatory cells injection; Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Everolimus; Procedure: Kidney transplantation |
| Immunosuppression | Active comparator | Patients will undergo immunosuppressive therapy followed by living related kidney transplantation Receives: Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Everolimus; Procedure: Kidney transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient and graft survival
Measured: At 1 years post-transplant
Secondary outcomes (4)
Patient and graft survival
Measured: At 3 years post-transplant
Incidence rate of biopsy-proven acute rejection, defined as a renal biopsy demonstrating acute cellular or humoral rejection of Banff Grade IA or greater
Measured: 3 years
Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24-hour urine protein excretion
Measured: 3 years
Incidence of adverse events associated with renal transplantation and immunosuppression
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionNov 2014 (estimated)
- Study completionNov 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pirogov Russian National Research Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Russian Academy of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Svetlana N. Bykovskaia, M.D. Ph.D., Principal investigator, Russian State Medical UniversityMichael M. Kaabak, M.D. Ph.D., Principal investigator, Boris Petrovsky's Scientific Center of Surgery Russian Academy of Medical Sciencies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446484
- Sponsor's protocol ID
- RSMU-001
- Status last verified
- Nov 2011
- First submitted
- 3 Oct 2011
- Last updated
- 18 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Pilot Study Using Autologous CD4+CD25+FoxP3+ T Regulatory Cells and Campath-1H to Induce Renal Transplant Tolerance
- ClinicalTrials.gov ID
- NCT01446484
- Acronym / sponsor ID
- RSMU-001
- Conditions
- End-Stage Renal Disease, Kidney Failure
- Keywords
- Renal transplantation, Kidney transplantation, CD4+CD25+CD127lowFoxP3+ T Regulatory Cells, T reg, Campath
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Pirogov Russian National Research Medical UniversityUniversity, hospital or other
- Collaborators
- Russian Academy of Medical Sciences
- Study start
- Oct 2011
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Nov 2014 (estimated)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T reg therapy | Experimental | Biological: CD4+CD25+CD127lowFoxP3+ T regulatory cells injection, Drug: Alemtuzumab, Drug: Mycophenolate mofetil, Drug: Sirolimus, Drug: Tacrolimus, Drug: Cyclosporine, Drug: Everolimus, Procedure: Kidney transplantationKidney transplantation, followed by immunotherapy given along with autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells infusions |
| Immunosuppression | Active comparator | Drug: Alemtuzumab, Drug: Mycophenolate mofetil, Drug: Sirolimus, Drug: Tacrolimus, Drug: Cyclosporine, Drug: Everolimus, Procedure: Kidney transplantationPatients will undergo immunosuppressive therapy followed by living related kidney transplantation |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD4+CD25+CD127lowFoxP3+ T regulatory cells injectionAlso: Cell therapyBlood 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 | Biological | T reg therapy |
| AlemtuzumabAlso: CampathImmunosuppressant; 2 doses of drug by intravenous infusion on Days 14 - 21 before Tx and on Day 0 after Tx | Drug | Immunosuppression, T reg therapy |
| Mycophenolate mofetilAlso: CellceptImmunosuppressant; oral daily dose starting Day 2-3 until withdrawal or end of the study | Drug | Immunosuppression, T reg therapy |
| SirolimusAlso: Rapamycin, RapamuneImmunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study | Drug | Immunosuppression, T reg therapy |
| TacrolimusAlso: PrografImmunosuppressant; daily dose starting Day 0 until withdrawal or end of the study | Drug | Immunosuppression, T reg therapy |
| CyclosporineAlso: NeoralImmunosuppressant; daily dose starting Day 0 until withdrawal or end of the study | Drug | Immunosuppression, T reg therapy |
| EverolimusAlso: Certican, AfinitorImmunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study | Drug | Immunosuppression, T reg therapy |
| Kidney transplantationAlso: Renal TransplantationLiving related kidney transplantation | Procedure or surgery | Immunosuppression, T reg therapy |
Primary outcome
Patient and graft survival
Time frame: At 1 years post-transplant
4 secondary outcomes
Patient and graft survival
Time frame: At 3 years post-transplant
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
Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24-hour urine protein excretion
Time frame: 3 years
Incidence of adverse events associated with renal transplantation and immunosuppression
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Svetlana N. Bykovskaia, M.D. Ph.D. principal investigator
Russian State Medical University
Michael M. Kaabak, M.D. Ph.D. principal investigator
Boris Petrovsky's Scientific Center of Surgery Russian Academy of Medical Sciencies
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CD4+CD25+CD127lowFoxP3+ T regulatory cells injection, Alemtuzumab and Mycophenolate mofetil in people with End-Stage Renal Disease and Kidney Failure, run by Pirogov Russian National Research Medical University at 2 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Svetlana N. Bykovskaia, M.D. Ph.D. (7-916-4362291, sbykovskaia@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient and graft survival (time frame: At 1 years post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2011.