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

NCT00183248 | Completed Phase 1 Results DMC

• 1 other identifier: DAIT ITN022ST
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplantation; Kidney Disease; Kidney Failure

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Participant Survival at One Year Post Kidney Transplant

  One year post kidney transplant

• Overall Kidney Graft Survival at One Year Post-Transplant

  Number of participants that did not experience kidney graft failure\[1\] at one year post-transplant \[1\]Graft failure is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation.

  One year post kidney transplant

Secondary Outcomes (5)

• Participant Survival at Three Years Post Kidney Transplant

  Three years post kidney transplant

• Graft Survival at Three Years Post-Transplant

  Three years post kidney transplant

• Number of Kidney Biopsy-proven Acute Rejection

  Three years post kidney transplant

• Number of Chronic Allograft Nephropathies

  Three years post kidney transplant

• Number of Graft-versus-host Disease (GVHD) Events

  Three years post kidney transplant

Study Arms (2)

DBMCs

EXPERIMENTAL

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

Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Donor bone marrow stem cell infusion; Procedure: Kidney transplant

Control Group

ACTIVE COMPARATOR

Kidney transplantation, followed by immunotherapy

Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Kidney transplant

Interventions

Alemtuzumab DRUG

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

Also known as: Campath

Control Group; DBMCs

Mycophenolate mofetil DRUG

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

Also known as: Cellcept

Control Group; DBMCs

Sirolimus DRUG

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

Also known as: rapamycin, Rapamune

Control Group; DBMCs

Tacrolimus DRUG

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

Also known as: FK-506

Control Group; DBMCs

Donor bone marrow stem cell infusion PROCEDURE

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

DBMCs

Kidney transplant PROCEDURE

Occurs at study entry

Control Group; DBMCs

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (1)

• 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.

  PMID: 23903014 DERIVED

Related Links

• Click here for the Immune Tolerance Network Web site

MeSH Terms

Conditions

Kidney Diseases; Renal Insufficiency; Bronchiolitis Obliterans Syndrome

Interventions

Alemtuzumab; Mycophenolic Acid; Sirolimus; Tacrolimus; Kidney Transplantation

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

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; Renal Replacement Therapy; Therapeutics; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Limitations and Caveats

In July 2007 after the trial had been enrolling for approximately 42 months, enrollment was stopped at the current number of nine subjects due to time and resource constraints.

Results Point of Contact

• Title: George W. Burke III, M.D.
• Organization: University of Miami

Gburke@med.miami.edu

(305) 355-5060

Study Officials

• George W. Burke, III, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: September 11, 2005
• First Posted: September 16, 2005
• Study Start: September 1, 2004
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: October 2, 2012
• Results First Posted: June 21, 2012

Record last verified: 2012-09

Locations

US (1)