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A Trial of Two Steroid-Free Approaches Toward Mycophenolate Mofetil-Based Monotherapy Immunosuppression (Cell220)

20. Oktober 2015 aktualisiert von: Joseph Leventhal, Northwestern University

A Phase IV, Single Center Pilot Study Using Alemtuzumab (Campath-1H) Induction Combined With Prednisone-Free, Calcineurin-Inhibitor-Free Immunosuppression in Kidney Transplantation

This is an open label, single-center, randomized phase IV pilot study of steroid and calcineurin inhibitor avoidance in renal transplant recipients. All patients will receive two doses of alemtuzumab to achieve peripheral T-cell depletion. Intravenous glucocorticoids will be administered prior to alemtuzumab administration to limit cytokine release syndrome in association with this monoclonal antibody, and continued for the first two days post-transplant. Thereafter, steroids will not be used for immunosuppression. All transplant recipients will be started on oral immunosuppressive therapy with mycophenolate mofetil (MMF) prior to transplant. Pretransplant, these patients will be randomized to receive, in addition, either tacrolimus (Tac) or sirolimus.

After six months, patients in the tacrolimus arm who do not experience rejection will be randomized to continue on tacrolimus or to be converted to the combination of sirolimus and MMF. Individuals in this arm of the study who do not experience acute rejection, and demonstrate evidence of donor specific hyporesponsiveness at 9 months post-transplant (those staying on Tac + MMF) or 3 months post-conversion (those converted from Tac + MMF to sirolimus + MMF) will be weaned to MMF monotherapy.

Individuals in the sirolimus + MMF arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesponsiveness at 6 months post-transplant will be weaned to MMF monotherapy.

Studienübersicht

Studientyp

Interventionell

Einschreibung (Tatsächlich)

40

Phase

  • Phase 4

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

    • Illinois
      • Chicago, Illinois, Vereinigte Staaten, 60611
        • Northwestern University/Northwestern Memorial Hospital

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 65 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  1. Patients who are male or female age 18-65 years
  2. Donor age 18-65 years
  3. Patients who are single-organ recipients (kidney only)
  4. Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period.
  5. Subject (recipient) is able to understand the consent form and give written informed consent

Exclusion Criteria:

  1. Known sensitivity or contraindication to sirolimus, tacrolimus or MMF
  2. Patient with significant or active infection
  3. Patients with a positive lymphocytotoxic crossmatch using donor lymphocytes and recipient serum
  4. Patients with PRA > 20%
  5. Patients who are pregnant or nursing mothers
  6. Patients whose life expectancy is severely limited by diseases other than renal disease
  7. Ongoing active substance abuse, drug or alcohol
  8. Major ongoing psychiatric illness or recent history of noncompliance
  9. Significant cardiovascular disease (e.g.):

    • Significant non-correctable coronary artery disease
    • Ejection fraction below 30%
    • History of recent myocardial infarction
  10. Malignancy within 3 years, excluding non-melanoma skin cancers
  11. Serologic evidence of infection with HIV or HBVsAg positive
  12. Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet count < 100,000/mm3; triglycerides > 400 mg/dl; total cholesterol > 300 mg/dl
  13. Investigational drug within 30 days prior to transplant surgery
  14. Anti-T cell therapy within 30 days prior to transplant surgery
  15. Patients using Prednisone
  16. Patients who are ABO incompatible

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: Group 1: Alemtuzumab + TAC + MMF
Receive two doses of alemtuzumab (Campath-1H, 30mg) by intravenous (IV) infusion. One dose during kidney transplant surgery and the second dose on day 2 (post-surgery) to achieve peripheral T-cell depletion. IV glucocorticoids will be given prior to Campath administration to limit cytokine release syndrome in association with this monoclonal antibody. MMF on the day of surgery and continue taking it by mouth, twice daily. TAC started on the 1st day after surgery, and then taken by mouth twice daily.
Tacrolimus (TAC) will be given standard of care by prescription twice a day (2.0 mg), orally. Doses will be adjusted by serum levels. The dose will be modified to achieve 12 hour trough concentrations of 5-8 ng/mL.
Andere Namen:
  • FK506
  • Prograf®
Patients receiving alemtuzumab will be premedicated with 50mg of diphenhydramine hydrochloride, and 650mg of acetaminophen 30-60 minutes to the first Alemtuzumab infusion. The of 30mg will be diluted in 100cc sterile 0.9% normal saline and infused over 2 hours. The infusion line must contain an in-line 0.22-micron filter. Alemtuzumab will be administered on the day of transplant (intraoperatively), and on post-operative day 2. Both doses will be administered while the patient is in the hospital. Alemtuzumab is supplied in single-use clear glass ampoules containing 30mg of alemtuzumab in 3mL of solution.
Andere Namen:
  • Campath-1H
  • Campath®
  • Mabcampath®
MMF will be given at 1.0-1.5gm, twice daily, orally. The first dose will be given pre-transplant, open label fashion.
Andere Namen:
  • Cellcept®
Aktiver Komparator: Group 2: Alemtuzumab + Sirolimus + MMF

Sirolimus will be taken by mouth before transplant surgery and will continue taking once daily after surgery. Group 2 will also receive 2 doses of Alemtuzumab: one during surgery and the second will be given on the second day after surgery. Mycophenolate mofetil will be give on the day of surgery and twice daily, by mouth, as instructed by the doctor.

If subjects do not experience kidney rejection after 6 months after surgery, they will be weaned off of the sirolimus and continue taking the mycophenolate mofetil.

Patients receiving alemtuzumab will be premedicated with 50mg of diphenhydramine hydrochloride, and 650mg of acetaminophen 30-60 minutes to the first Alemtuzumab infusion. The of 30mg will be diluted in 100cc sterile 0.9% normal saline and infused over 2 hours. The infusion line must contain an in-line 0.22-micron filter. Alemtuzumab will be administered on the day of transplant (intraoperatively), and on post-operative day 2. Both doses will be administered while the patient is in the hospital. Alemtuzumab is supplied in single-use clear glass ampoules containing 30mg of alemtuzumab in 3mL of solution.
Andere Namen:
  • Campath-1H
  • Campath®
  • Mabcampath®
MMF will be given at 1.0-1.5gm, twice daily, orally. The first dose will be given pre-transplant, open label fashion.
Andere Namen:
  • Cellcept®
Sirolimus will be given standard of care by prescription, dosed at 5mg daily. The dosage will be adjusted by serum level to achieve 24 hour trough concentrations of 8-12 ng/mL by HPLC assay.
Andere Namen:
  • Rapamycin
  • Rapamune®

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
The Incidence of Biopsy-proven Acute Allograft Rejection During the First 12 Months of Transplant.
Zeitfenster: Within 12 months post kidney transplant
The incidence of rejection is determined by the proportion of patients experiencing biopsy proven acute allograft rejection during the first 12 months post-transplant.
Within 12 months post kidney transplant

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Severity of Acute Rejection During the First 6 and 12 Months Post-transplant
Zeitfenster: Months 6-12 post-transplant
The diagnosis of rejection will be based on clinical symptoms and signs, laboratory tests, and confirmed by core renal allograft biopsy.
Months 6-12 post-transplant
Renal Function at 12 Months Post-transplant
Zeitfenster: At 12 months post-transplant
Laboratory tests for renal function include creatinine or iothalamate glomerular filtration rate (GFR).
At 12 months post-transplant
Incidence of Donor Specific Hyporesponsiveness Allowing for the Conversion to Monotherapy
Zeitfenster: At 6 & 9 months post-transplant
The proportion of subjects for both groups determine this measure: 1) Patients in tacrolimus arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesonsiveness at 9 months post-transplant (those staying on TAC+MMF) or 3 months post-convertion (converted from TAC+MMF to Sirolimus+MMF) will be weaned to MMF monotherapy; 2) Those in the sirolimus+MMF arm who do not experience acute rejection and demonstrate evidence of donor specific hyporesponsiveness at 6 months post-transplant will be weaned to MMF monotherapy.
At 6 & 9 months post-transplant
Patient and Graft Survival Rates at 6 and 12 Months Post-transplant
Zeitfenster: At 6 & 12 months post-transplant
At 6 & 12 months post-transplant

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Mitarbeiter

Ermittler

  • Hauptermittler: Joseph R Leventhal, MD, PhD, Northwestern University

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. April 2005

Primärer Abschluss (Tatsächlich)

1. April 2010

Studienabschluss (Tatsächlich)

1. April 2010

Studienanmeldedaten

Zuerst eingereicht

9. September 2005

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

9. September 2005

Zuerst gepostet (Schätzen)

14. September 2005

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

26. Oktober 2015

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

20. Oktober 2015

Zuletzt verifiziert

1. Oktober 2015

Mehr Informationen

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