Using Donor Stem Cells and Alemtuzumab to Prevent Organ Rejection in Kidney Transplant Patients

NCT ID: NCT00183248

Last Updated: 2012-10-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2009-11-30

Brief Summary

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Alemtuzumab is a man-made antibody used to treat certain blood disorders. This study will evaluate treatment of kidney transplant recipients with alemtuzumab and other immune system suppressing medications with or without infusions of bone marrow stem cells from the kidney donor. The purpose of this study is to find out which strategy is more effective in preventing organ rejection and maintaining patient health.

Detailed Description

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Organ transplantation is a common procedure in hospitals, but organ rejection and serious side effects are potential problems for the patient. Mycophenolate mofetil, sirolimus, and tacrolimus are drugs used to decrease immune system activity in people who have received organ transplants so that the new organ will not be rejected. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. In this study, alemtuzumab will be used to destroy the recipient's white blood cells (WBCs) at the time of transplantation. It is hoped that WBCs produced after alemtuzumab administration will recognize the transplanted liver as "self" and will not attack the new kidney.

To further assist the immune system in accepting the donor kidney, some patients in this study will also receive two infusions of bone marrow stem cells from the kidney donor. Bone marrow stem cells are adult blood cells from which other specialized blood cells, such as T cells, develop. Treatment with these cells is believed to create a state of "chimerism" in the body, where the immune cells of both the donor and recipient can coexist and tolerate the presence of a donor organ. This study will evaluate the safety and effectiveness of an antirejection regimen including alemtuzumab and other immunosuppressive medications and donor bone marrow stem cell infusions in patients undergoing kidney transplantation.

This study will last 3 years. Participants will be randomly assigned to receive either the full immunosuppressive therapy and donor bone marrow stem cell infusions (Group 1) or immunosuppressive therapy alone (Group 2). Patients will undergo kidney transplantation at the start of the study on Day 0. Patients will receive inpatient infusions of alemtuzumab on Days 0 and 4. Starting on Day 0, patients will begin taking mycophenolate mofetil; starting on Day 1, patients will also begin taking tacrolimus. On Day 5, patients in Group 1 will receive their first of 2 infusions of purified stem cells taken from the kidney donor's bone marrow; their second infusion of stem cells will occur sometime between Months 4 and 6 post-transplant.

Beginning between Months 4 and 6 post-transplant, all participants will begin receiving low-dose maintenance immunosuppressive therapy with sirolimus, as is typical for post-transplant antirejection therapy. One year post-transplant, patients will be evaluated for the potential to withdraw some or all of this maintenance immunotherapy. Participants will be monitored for 3 years post-transplant. Urine collection will occur at Week 1 and Months 1, 3, 6, and 9. At Months 12, 24, and 30, participants will undergo kidney biopsies. Blood collection will occur at regular intervals for laboratory tests to evaluate the immune system's response to the transplanted kidney.

Conditions

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Kidney Transplantation Kidney Disease Kidney Failure

Keywords

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kidney kidney transplant kidney transplantation transplant transplantation renal renal transplant renal transplantation kidney disease chronic renal failure kidney failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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DBMCs

Kidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type DRUG

Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4

Mycophenolate mofetil

Intervention Type DRUG

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

Sirolimus

Intervention Type DRUG

Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study

Tacrolimus

Intervention Type DRUG

Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study

Donor bone marrow stem cell infusion

Intervention Type PROCEDURE

2 doses of kidney donor's bone marrow stem cells by IV infusion on Day 5 and sometime between Months 4 and 6

Kidney transplant

Intervention Type PROCEDURE

Occurs at study entry

Control Group

Kidney transplantation, followed by immunotherapy

Group Type ACTIVE_COMPARATOR

Alemtuzumab

Intervention Type DRUG

Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4

Mycophenolate mofetil

Intervention Type DRUG

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

Sirolimus

Intervention Type DRUG

Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study

Tacrolimus

Intervention Type DRUG

Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study

Kidney transplant

Intervention Type PROCEDURE

Occurs at study entry

Interventions

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Alemtuzumab

Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4

Intervention Type DRUG

Mycophenolate mofetil

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

Intervention Type DRUG

Sirolimus

Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study

Intervention Type DRUG

Tacrolimus

Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study

Intervention Type DRUG

Donor bone marrow stem cell infusion

2 doses of kidney donor's bone marrow stem cells by IV infusion on Day 5 and sometime between Months 4 and 6

Intervention Type PROCEDURE

Kidney transplant

Occurs at study entry

Intervention Type PROCEDURE

Other Intervention Names

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Campath Cellcept rapamycin, Rapamune FK-506

Eligibility Criteria

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Inclusion Criteria

* Weight greater than 40 kg (88.2 lbs)
* Will be receiving a living-related (1-haplotype-matched donor/recipient) primary kidney allograft
* Negative B-cell and T-cell cytotoxic and flow cytometry crossmatch (1-haplotype-matched donor/recipient pairs with a minimum of 1 HLA DR 1A and 1B locus in common and panel-reactive antibodies \[PRA\] of less than 10%)
* 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
* Willing to comply with the study visits
* Willing to use acceptable forms of contraception

Exclusion Criteria

* Previously received or is receiving an organ transplant other than a kidney
* Receiving an ABO (blood type) incompatible donor kidney
* Human Immunodeficiency Virus (HIV) infected
* Antibody positive for hepatitis C virus (HCV)
* Surface antigen positive for hepatitis B virus (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 aspartate aminotransferase (AST SGOT) or alanine aminotransferase (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, thymoglobulin daclizumab, or corticosteroids
* Certain screening laboratory values. More information on this criterion can be found in the protocol.
* Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study
* Anticipated contraindication to tacrolimus administration for longer than 5 days post-transplant
* Currently undergoing peritoneal dialysis
* PRA value less than 10% at any time prior to study entry
* Graves disease. Patients with Graves disease adequately treated with radioiodine ablative therapy are not excluded.
* Cytomegalovirus (CMV) or Epstein-Barr virus (EBV) negative kidney recipient receiving a kidney from a CMV or EBV positive donor
* Pregnancy or breastfeeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role lead

Responsible Party

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George W. Burke

Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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George W. Burke, III, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of Miami

Miami, Florida, United States

Site Status

Countries

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United States

References

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Ciancio G, Sageshima J, Akpinar E, Gaynor JJ, Chen L, Zarak A, Hanson L, Tueros L, Guerra G, Mattiazzi A, Kupin W, Roth D, Ricordi C, Burke GW 3rd. A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab. Transplantation. 2013 Nov 15;96(9):800-6. doi: 10.1097/TP.0b013e3182a0f68c.

Reference Type DERIVED
PMID: 23903014 (View on PubMed)

Related Links

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http://www.immunetolerance.org

Click here for the Immune Tolerance Network Web site

Other Identifiers

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DAIT ITN022ST

Identifier Type: -

Identifier Source: org_study_id