- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00240994
Safety in Immunomodulatory Functions of Alemtuzumab (Campath) in Pediatric Kidney Transplantation Recipients
A Phase II Exploratory Study to Determine the Safety and Study the Immunomodulatory Functions of Induction Therapy With Campath, Combined With Chronic Immunosuppression With Mycophenolate Mofetil and Sirolimus
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.
The accrual period is scheduled for 18 months. The study follow-up period will last 24 months. All participants enrolled will undergo this treatment schedule: 1.) All participants will receive intravenous alemtuzumab one day before transplantation and 1 day after transplantation. 2.) Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. 3.) Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when 4.) Sirolimus will be initiated. 5.) Sirolimus and MMF will be taken orally until Month 24.
Blood collection will occur at baseline, 1 day before transplant, at Days 1 and 3, at Weeks 2, 4, 6, 8, 10, and at Months 3 through 24. Scheduled kidney (renal) biopsies will be performed at transplant, during Weeks 8 through 12, immediately before conversion to sirolimus, and at Months 6 and 24.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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California
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San Francisco, California, États-Unis, 94143-0116
- University of California, San Francisco
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Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Children's Hospital, Boston
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19104
- Children's Hospital, Philadelphia
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Washington
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Seattle, Washington, États-Unis, 98105
- Children's Hospital and Regional Medical Center, Seattle
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Between the ages of 1 to 20 (prior to 21st birthday)
- End Stage Renal Disease
- Necessity of kidney transplant
- First kidney transplant received from a living donor
- A living kidney donor identified
- No known contraindications to therapy with alemtuzumab
- Negative pregnancy test before study entry
- Willing to use approved methods of contraception for the duration of the study, 6 weeks after discontinuation of MMF, and 12 weeks after discontinuation of sirolimus
- Informed consent from participant, parent, or guardian
- Current vaccinations, including varicella-zoster (VZV) vaccine, before study enrollment
Exclusion Criteria:
- Recipient of a deceased donor kidney transplant
- Multiorgan transplant
- History of prior organ transplantation
- Participant sensitized to greater than 0% Panel Reactive Antibody (PRA) within 4 weeks before study enrollment. (If participant receives a blood transfusion status post PRA test, then the PRA must be repeated within 1 week of transplantation)
- Participants with human leukocyte antigen (HLA) identical living related donors
- History of primary focal segmented glomerulosclerosis
- History of other disorders requiring continuous maintenance steroids or calcineurin inhibitors
- Active systemic infection at time of transplant
- History of malignancy
- Infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Contraindication to receive tacrolimus, sirolimus, MMF, or monoclonal antibody therapy
- Use of investigational drugs within 4 weeks before study enrollment
- Recipient of any licensed or investigational live attenuated vaccine(s) within 2 months before study enrollment
- Family history of high cholesterol
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Alemtuzumab (Campath)
In this open-label, single-arm trial , participants will be administered a 0.3 mg/kg dose of alemtuzumab (Campath) intravenously one day prior to kidney transplantation and one day post kidney transplantation.
Participants will then receive a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
|
Administered intravenously over a period of 2-3 hours.
Two doses total, the first will be one day before transplant and the second will be on the day following transplantation.
Pre-medication with methylprednisolone, acetaminophen, and Benadryl will be administered before each dose.
Autres noms:
Administered orally at a dose of 0.05-0.1 mg/kg twice daily, beginning 1-3 days following transplantation and continuing until weeks 8-12.
Tacrolimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible.
Autres noms:
Per recommendation
Autres noms:
Administered by either liquid or tablet every 12 hours from month 6 until month 24.
Dosage will vary throughout the treatment course.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
Délai: Up to one year post kidney transplantation procedure
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Graft loss is defined as the need for dialysis for more than 30 days duration, allograft nephrectomy, or the decision to withdraw immunosuppression due to graft failure.
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Up to one year post kidney transplantation procedure
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Collaborateurs et enquêteurs
Collaborateurs
Les enquêteurs
- Chaise d'étude: William Harmon, MD, Boston Children's Hospital
Publications et liens utiles
Publications générales
- Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53. doi: 10.1111/j.1600-6143.2005.00822.x.
- Wolff G, Strecker K, Vester U, Latta K, Ehrich JH. Non-compliance following renal transplantation in children and adolescents. Pediatr Nephrol. 1998 Nov;12(9):703-8. doi: 10.1007/s004670050531.
- Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roohipour R, Carreno MR, Roth D, Ruiz P, Kupin W, Rosen A, Esquenazi V, Tzakis AG, Miller J. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation. 2004 Aug 15;78(3):426-33. doi: 10.1097/01.tp.0000128625.29654.eb.
- Rao V, Pirsch JD, Becker BN, Knechtle SJ. Sirolimus monotherapy following Campath-1H induction. Transplant Proc. 2003 May;35(3 Suppl):128S-130S. doi: 10.1016/s0041-1345(03)00227-6.
- Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60. doi: 10.1097/00007890-200004150-00009.
- De Serres SA, Mfarrej BG, Magee CN, Benitez F, Ashoor I, Sayegh MH, Harmon WE, Najafian N. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol. 2012 Jan;23(1):174-82. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies rénales
- Maladies urologiques
- Insuffisance rénale chronique
- Insuffisance rénale chronique
- Insuffisance rénale
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques immunologiques
- Agents antibactériens
- Antibiotiques, Antinéoplasiques
- Agents antifongiques
- Agents antituberculeux
- Antibiotiques, Antituberculeux
- Inhibiteurs de la calcineurine
- Tacrolimus
- Acide mycophénolique
- Sirolimus
- Alemtuzumab
Autres numéros d'identification d'étude
- DAIT PC01
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Données/documents d'étude
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Ensemble de données de participant individuel
Identifiant des informations: SDY134Commentaires d'informations: ImmPort study identifier is SDY134
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Protocole d'étude
Identifiant des informations: SDY134Commentaires d'informations: ImmPort study identifier is SDY134
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Study summary, - schedule of events, -download packages et al.
Identifiant des informations: SDY134Commentaires d'informations: ImmPort study identifier is SDY134
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 .
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