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

17 settembre 2012 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

9

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Florida
      • Miami, Florida, Stati Uniti, 33136
        • University of Miami

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 65 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Separare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: DBMCs
Kidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions
Droga: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Altri nomi:
  • Campath
Droga: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Altri nomi:
  • Cellcept
Droga: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Altri nomi:
  • rapamycin, Rapamune
Droga: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Altri nomi:
  • FK-506
Procedura: 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
Procedura: Kidney transplant
Occurs at study entry
Comparatore attivo: Control Group
Kidney transplantation, followed by immunotherapy
Droga: Alemtuzumab
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
Altri nomi:
  • Campath
Droga: Mycophenolate mofetil
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
Altri nomi:
  • Cellcept
Droga: Sirolimus
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
Altri nomi:
  • rapamycin, Rapamune
Droga: Tacrolimus
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
Altri nomi:
  • FK-506
Procedura: Kidney transplant
Occurs at study entry

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall Participant Survival at One Year Post Kidney Transplant
Lasso di tempo: One year post kidney transplant
One year post kidney transplant
Overall Kidney Graft Survival at One Year Post-Transplant
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Participant Survival at Three Years Post Kidney Transplant
Lasso di tempo: Three years post kidney transplant
Three years post kidney transplant
Graft Survival at Three Years Post-Transplant
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University of Miami

Collaboratori

Immune Tolerance Network (ITN)

Investigatori

  • Investigatore principale: George W. Burke, III, MD, University of Miami

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2004

Completamento primario (Effettivo)

1 novembre 2009

Completamento dello studio (Effettivo)

1 novembre 2009

Date di iscrizione allo studio

Primo inviato

11 settembre 2005

Primo inviato che soddisfa i criteri di controllo qualità

11 settembre 2005

Primo Inserito (Stima)

16 settembre 2005

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

2 ottobre 2012

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 settembre 2012

Ultimo verificato

1 settembre 2012

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • DAIT ITN022ST

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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