Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant
Renal Allograft Tolerance Through Mixed Chimerism (ITN010ST)
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
-
Massachusetts
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Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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. |
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.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Graft Survival Twenty-Four Months Post Transplantation
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Participant Survival
Časové okno: 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
Časové okno: Up to thirty-six months (3 Years) Post Transplantation
|
During the three-year post-transplant follow-up period for enrolled participants.
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Up to thirty-six months (3 Years) Post Transplantation
|
|
Change from Baseline in Renal Function Using Serum Creatinine
Časové okno: Up to thirty-six months (3 Years) Post Transplantation
|
Changes in serum creatinine levels from baseline through post transplantation follow-up period.
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Up to thirty-six months (3 Years) Post Transplantation
|
|
Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)
Časové okno: 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
Časové okno: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
|
As defined by protocol.
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Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
|
Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: David H. Sachs, MD, Department of Medicine, Massachusetts General Hospital
- Vrchní vyšetřovatel: A. Benedict Cosimi, MD, Department of Medicine, Massachusetts General Hospital
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- DAIT ITN010ST
- DAIT NKD03 (Jiný identifikátor: Immune Tolerance Network)
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