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

22 décembre 2017 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

5

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02114
        • Massachusetts General Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 55 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: 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.
Autres noms:
  • nonmyeloablative preparative regimen

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Graft Survival Twenty-Four Months Post Transplantation
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Participant Survival
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
As defined by protocol.
Participant enrollment through <=thirty-six months (3 Years) Post Transplantation

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborateurs

Immune Tolerance Network (ITN)

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 juin 2003

Achèvement primaire (Réel)

1 janvier 2009

Achèvement de l'étude (Réel)

1 juillet 2009

Dates d'inscription aux études

Première soumission

7 juillet 2003

Première soumission répondant aux critères de contrôle qualité

7 juillet 2003

Première publication (Estimation)

8 juillet 2003

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

27 décembre 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 décembre 2017

Dernière vérification

1 décembre 2017

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • DAIT ITN010ST
  • DAIT NKD03 (Autre identifiant: Immune Tolerance Network)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

Essais cliniques sur Transplantation rénale

  • Abramson Cancer Center of the University of Pennsylvania
    Retiré
    ECR d'ACP pour la transplantation
    Patients cancéreux subissant une greffe de cellules souches (RCT of ACP for Transplant)

Essais cliniques sur Conditioning Regimen

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Conditions

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Commanditaire / collaborateurs

Emplacements

3
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