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Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant

22 dicembre 2017 aggiornato da: National Institute of Allergy and Infectious Diseases (NIAID)

Renal Allograft Tolerance Through Mixed Chimerism (ITN010ST)

This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, participants must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.

Participants in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, participants will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether participants with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.

Participants will be assessed before and after transplantation and will be followed ≤36 months.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

5

Fase

  • 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
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02114
        • Massachusetts General Hospital

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 55 anni (Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] greater than 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA, and flow cytometry;
  • Undergoing a first or second transplant;
  • Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing);
  • Cardiac ejection fraction greater than 40%;
  • Forced expiratory volume (FEV1) greater than 50%;
  • Liver function tests, bilirubin, and coagulation studies less than 2 X normal;
  • White blood cells greater than 2000/mm^3; abd
  • Platelets greater than 100,000/mm^3

Exclusion Criteria:

  • Positive donor lymphocyte cross-match;
  • HIV-1 infected;
  • Positive hepatitis B surface antigen (HbsAg);
  • Hepatitis C virus infected;
  • History of cancer;
  • Prior dose-limiting radiation therapy;
  • Pregnant, breastfeeding, or planning pregnancy within the time frame of the study;
  • Enrolled in another investigational drug study within 30 days prior to study entry; or
  • Receiving maintenance immunosuppression within 3 months before the conditioning regimen begins

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: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Conditioning Regimen

Cyclophosphamide intravenously (IV) on days -5 and -4 with respect to transplantation; MEDI-507 on days -1, 0, and 1 (after a test dose of 0.1 mg per kg on day -2); and cyclosporine A IV and thymic irradiation on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered daily postoperatively, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months.

Amendment applicable to the 4th and 5th participant: rituximab on days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.
Droga: Conditioning Regimen
Cyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.
Altri nomi:
  • nonmyeloablative preparative regimen

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Graft Survival Twenty-Four Months Post Transplantation
Lasso di tempo: 24 months (2 Years) Post Transplantation
Defined by kidney transplant survival at month 24 post transplantation with successful withdrawal of cyclosporine following transplantation, in the absence of maintenance immunosuppression.
24 months (2 Years) Post Transplantation

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Participant Survival
Lasso di tempo: Up to thirty-six months (3 Years) Post Transplantation
During the three-year post-transplant follow-up period for enrolled participants.
Up to thirty-six months (3 Years) Post Transplantation
Graft Survival
Lasso di tempo: Up to thirty-six months (3 Years) Post Transplantation
During the three-year post-transplant follow-up period for enrolled participants.
Up to thirty-six months (3 Years) Post Transplantation
Change from Baseline in Renal Function Using Serum Creatinine
Lasso di tempo: Up to thirty-six months (3 Years) Post Transplantation
Changes in serum creatinine levels from baseline through post transplantation follow-up period.
Up to thirty-six months (3 Years) Post Transplantation
Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)
Lasso di tempo: From Week 1 through thirty-six months (3 Years) Post Transplantation
Evaluations for suspected GVHD, including biopsies as appropriate, during routine and/or for cause assessments.
From Week 1 through thirty-six months (3 Years) Post Transplantation
Number of Adverse Events
Lasso di tempo: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
As defined by protocol.
Participant enrollment through <=thirty-six months (3 Years) Post Transplantation

Collaboratori e investigatori

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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaboratori

Immune Tolerance Network (ITN)

Investigatori

  • Investigatore principale: David H. Sachs, MD, Department of Medicine, Massachusetts General Hospital
  • Investigatore principale: A. Benedict Cosimi, MD, Department of Medicine, Massachusetts General Hospital

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 giugno 2003

Completamento primario (Effettivo)

1 gennaio 2009

Completamento dello studio (Effettivo)

1 luglio 2009

Date di iscrizione allo studio

Primo inviato

7 luglio 2003

Primo inviato che soddisfa i criteri di controllo qualità

7 luglio 2003

Primo Inserito (Stima)

8 luglio 2003

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

27 dicembre 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

22 dicembre 2017

Ultimo verificato

1 dicembre 2017

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • DAIT ITN010ST
  • DAIT NKD03 (Altro identificatore: Immune Tolerance Network)

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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