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

17. září 2012 aktualizováno: 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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

9

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Spojené státy
    • Florida
      • Miami, Florida, Spojené státy, 33136
        • University of Miami

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 65 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Singl

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: DBMCs
Kidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions
Lék: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Ostatní jména:
  • Camppath
Lék: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Ostatní jména:
  • Cellcept
Lék: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Ostatní jména:
  • rapamycin, Rapamune
Lék: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Ostatní jména:
  • FK-506
Postup: 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
Postup: Kidney transplant
Occurs at study entry
Aktivní komparátor: Control Group
Kidney transplantation, followed by immunotherapy
Lék: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Ostatní jména:
  • Camppath
Lék: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Ostatní jména:
  • Cellcept
Lék: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Ostatní jména:
  • rapamycin, Rapamune
Lék: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Ostatní jména:
  • FK-506
Postup: Kidney transplant
Occurs at study entry

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Overall Participant Survival at One Year Post Kidney Transplant
Časové okno: One year post kidney transplant
One year post kidney transplant
Overall Kidney Graft Survival at One Year Post-Transplant
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Participant Survival at Three Years Post Kidney Transplant
Časové okno: Three years post kidney transplant
Three years post kidney transplant
Graft Survival at Three Years Post-Transplant
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

University of Miami

Spolupracovníci

Immune Tolerance Network (ITN)

Vyšetřovatelé

  • Vrchní vyšetřovatel: George W. Burke, III, MD, University of Miami

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. září 2004

Primární dokončení (Aktuální)

1. listopadu 2009

Dokončení studie (Aktuální)

1. listopadu 2009

Termíny zápisu do studia

První předloženo

11. září 2005

První předloženo, které splnilo kritéria kontroly kvality

11. září 2005

První zveřejněno (Odhad)

16. září 2005

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

2. října 2012

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

17. září 2012

Naposledy ověřeno

1. září 2012

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • DAIT ITN022ST

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