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

17. september 2012 opdateret af: George W. Burke, University of Miami

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

9

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Florida
      • Miami, Florida, Forenede Stater, 33136
        • University of Miami

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 65 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: DBMCs
Kidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions
Medicin: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Andre navne:
  • Campath
Medicin: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Andre navne:
  • Cellcept
Medicin: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Andre navne:
  • rapamycin, Rapamune
Medicin: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Andre navne:
  • FK-506
Procedure: 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
Procedure: Kidney transplant
Occurs at study entry
Aktiv komparator: Control Group
Kidney transplantation, followed by immunotherapy
Medicin: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Andre navne:
  • Campath
Medicin: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Andre navne:
  • Cellcept
Medicin: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Andre navne:
  • rapamycin, Rapamune
Medicin: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Andre navne:
  • FK-506
Procedure: Kidney transplant
Occurs at study entry

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Participant Survival at One Year Post Kidney Transplant
Tidsramme: One year post kidney transplant
One year post kidney transplant
Overall Kidney Graft Survival at One Year Post-Transplant
Tidsramme: One year post kidney 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Participant Survival at Three Years Post Kidney Transplant
Tidsramme: Three years post kidney transplant
Three years post kidney transplant
Graft Survival at Three Years Post-Transplant
Tidsramme: Three years post kidney 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.
Three years post kidney transplant
Number of Kidney Biopsy-proven Acute Rejection
Tidsramme: Three years post kidney transplant

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
Three years post kidney transplant
Number of Chronic Allograft Nephropathies
Tidsramme: Three years post kidney transplant

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
Three years post kidney transplant
Number of Graft-versus-host Disease (GVHD) Events
Tidsramme: Three years post kidney transplant
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.
Three years post kidney transplant

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Miami

Samarbejdspartnere

Immune Tolerance Network (ITN)

Efterforskere

  • Ledende efterforsker: George W. Burke, III, MD, University of Miami

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. september 2004

Primær færdiggørelse (Faktiske)

1. november 2009

Studieafslutning (Faktiske)

1. november 2009

Datoer for studieregistrering

Først indsendt

11. september 2005

Først indsendt, der opfyldte QC-kriterier

11. september 2005

Først opslået (Skøn)

16. september 2005

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

2. oktober 2012

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

17. september 2012

Sidst verificeret

1. september 2012

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • DAIT ITN022ST

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