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

NCT01446484 | Unknown Phase 1

• 1 other identifier: RSMU-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

End-Stage Renal Disease; Kidney Failure

Keywords

Renal transplantation; Kidney transplantation; CD4+CD25+CD127lowFoxP3+ T Regulatory Cells; T reg; Campath

Outcome Measures

Primary Outcomes (1)

• Patient and graft survival

  At 1 years post-transplant

Secondary Outcomes (4)

• Patient and graft survival

  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

  3 years

• Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24-hour urine protein excretion

  3 years

• Incidence of adverse events associated with renal transplantation and immunosuppression

  3 years

Study Arms (2)

T reg therapy

EXPERIMENTAL

Kidney transplantation, followed by immunotherapy given along with autologous CD4+CD25+CD127lowFoxP3+ T regulatory cells infusions

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

Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Everolimus; Procedure: Kidney transplantation

Interventions

CD4+CD25+CD127lowFoxP3+ T regulatory cells injection BIOLOGICAL

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

Also known as: Cell therapy

T reg therapy

Alemtuzumab DRUG

Immunosuppressant; 2 doses of drug by intravenous infusion on Days 14 - 21 before Tx and on Day 0 after Tx

Also known as: Campath

Immunosuppression; T reg therapy

Mycophenolate mofetil DRUG

Immunosuppressant; oral daily dose starting Day 2-3 until withdrawal or end of the study

Also known as: Cellcept

Immunosuppression; T reg therapy

Sirolimus DRUG

Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study

Also known as: Rapamycin, Rapamune

Immunosuppression; T reg therapy

Tacrolimus DRUG

Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study

Also known as: Prograf

Immunosuppression; T reg therapy

Cyclosporine DRUG

Immunosuppressant; daily dose starting Day 0 until withdrawal or end of the study

Also known as: Neoral

Immunosuppression; T reg therapy

Everolimus DRUG

Immunosuppressant; oral daily dose starting no earlier then after Month 1 post-transplant until withdrawal or end of the study

Also known as: Certican, Afinitor

Immunosuppression; T reg therapy

Kidney transplantation PROCEDURE

Living related kidney transplantation

Also known as: Renal Transplantation

Immunosuppression; T reg therapy

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pirogov Russian National Research Medical University: lead
• Russian Academy of Medical Sciences: collaborator

Study Sites (2)

The Russian State Medical University

Moscow, 117997, Russia

RECRUITING

Boris Petrovsky Scientific Center of Surgery Russian Academy of Medical Sciencies

Moscow, 119991, Russia

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency

Interventions

Cell- and Tissue-Based Therapy; Alemtuzumab; Mycophenolic Acid; Sirolimus; Tacrolimus; Cyclosporine; Everolimus; Kidney Transplantation

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Renal Replacement Therapy; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Svetlana N. Bykovskaia, M.D. Ph.D.

CONTACT

7-916-4362291; sbykovskaia@gmail.com

Anton A. Keskinov, Ph.D.

CONTACT

7-495-4341444; a.keskinov@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 5, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 18, 2011

Record last verified: 2011-11

Locations

RU (2)