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Kidney TransplantationPhase 1/2NCT00183248

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

A Phase 1/2 study testing Alemtuzumab, Mycophenolate mofetil and Sirolimus in people with Kidney Transplantation and Kidney Disease, run by University of Miami at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Alemtuzumab, Mycophenolate mofetil and Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Sep 2004to Nov 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 22Show 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 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Miami

    Miami, Florida, 33136

Other trials in United States

About this study

Official title: Pilot Study Using Donor Stem Cells and Campath-1H to Induce Renal Transplant Tolerance (ITN022ST)

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.

Read the detailed description

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.

Being tested
Alemtuzumab, Mycophenolate mofetil, Sirolimus, Tacrolimus, Donor bone marrow stem cell infusion
Keywords
kidney, kidney transplant, kidney transplantation, transplant, transplantation, renal, renal transplant, renal transplantation, kidney disease, chronic, renal failure, kidney failure
Medical subject headings
Kidney Diseases, Renal Insufficiency, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabDrug

    Also called Campath

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

  • Mycophenolate mofetilDrug

    Also called Cellcept

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

  • SirolimusDrug

    Also called rapamycin, Rapamune

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

  • TacrolimusDrug

    Also called FK-506

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

  • Donor bone marrow stem cell infusionProcedure or surgery

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

  • Kidney transplantProcedure or surgery

    Occurs at study entry

Study groups in NCT00183248
Study groupRoleWhat they receive
DBMCsExperimentalKidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions
Receives: Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Donor bone marrow stem cell infusion; Procedure: Kidney transplant
Control GroupActive comparatorKidney transplantation, followed by immunotherapy
Receives: Drug: Alemtuzumab; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Kidney transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Participant Survival at One Year Post Kidney Transplant

    Measured: One year post kidney transplant

  2. 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.

    Measured: One year post kidney transplant

Secondary outcomes (5)

  1. Participant Survival at Three Years Post Kidney Transplant

    Measured: Three years post kidney transplant

  2. Graft Survival at Three Years Post-Transplant

    Number of participants that did not experience kidney graft failure[1] at three years 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.

    Measured: Three years post kidney transplant

  3. Number of Kidney Biopsy-proven Acute Rejection

    Biopsy-proven acute renal (kidney) rejection[1,2].

    1. Diagnosis of acute rejection was made by renal biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection[2]
    2. Ref: Racusen LC et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999

    Measured: Three years post kidney transplant

  4. Number of Chronic Allograft Nephropathies

    Number of chronic allograft nephropathies[1,2,3] at 3 years post kidney transplant.

    1. Chronic allograft nephropathy is defined as renal biopsies with Banff 97 Grade I or greater[2] with higher numeric scores indicating more severe nephropathy
    2. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification[3]
    3. Reference: Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999

    Measured: Three years post kidney transplant

  5. Number of Graft-versus-host Disease (GVHD) Events

    A disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Symptoms include jaundice, skin rash or blisters, a dry mouth, or dry eyes. Also called graft-versus-host disease.

    Measured: Three years post kidney transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2005 (estimated)
  2. Study startSep 2004
  3. Primary completionNov 2009
  4. Study completionNov 2009

Resources

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
Single blind
Who is masked
Participant
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00183248
Sponsor's protocol ID
DAIT ITN022ST
Status last verified
Sep 2012
First submitted
11 Sep 2005
Last updated
2 Oct 2012
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23903014

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alemtuzumab, Mycophenolate mofetil and Sirolimus in people with Kidney Transplantation and Kidney Disease, run by University of Miami at 1 site in United States.

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 7 inclusion and 22 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: finished, as of the sponsor's last update on 2 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 21 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Participant Survival at One Year Post Kidney Transplant (time frame: One year post kidney transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00183248, which also lists 1 linked publication.

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 2 Oct 2012.

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