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Disease Prevention |
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Clinical Trial: Prevention of the Graft-Versus-Host-Disease in Patients After Stem Cell Transplantation with Tacrolimus and Everolimus
This study is not yet open for patient recruitment.
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Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Graft vs Host Disease | Drug: Tacrolimus Drug: Everolimus | Phase II Phase III |
MedlinePlus related topics: Immune System and Disorders
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Prophylaxis of the Graft-Versus-Host-Disease in Patients After Allogeneic Stem Cell Transplantation with a Combination of Tacrolimus and Everolimus
Secondary Outcomes: Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0); Hypersensitivity reactions; Hypertension; Hepatic toxicity (ASAT, bilirubin); Renal/urogenital toxicity (creatinine, cystitis); Acute gastrointestinal toxicity (mucositis, diarrhea); Thrombotic thrombocytopenic purpura; Hyperlipidemia; Neutropenia (duration); Efficacy; Grading of the acute GvHD; Incidence and grading of the chronic GvHD; Total and relapse-free survival rate one year after the stem cell transplantation
Expected Total Enrollment: 30
Study start: July 2005; Expected completion: June 2007
Last follow-up: January 2007; Data entry closure: March 2007
Eligibility
Inclusion Criteria:
- Male and female patients between 18 and 70 years of age
- Planned allogeneic stem cell transplantation either from a related or an unrelated donor
- Written informed consent
Exclusion Criteria:
- Previous stem cell transplantation
- Use of antibody Campath (anti CD-52) or ATG during the conditioning
- In vitro T-cell depleted graft
- Known hypersensitivity to everolimus or other constituents of the study medication
- Symptomatic infectious disease
- Hepatic disease (ASAT > 2 x ULN)
- Renal insufficiency (creatinine > 2 x ULN)
- HIV infection
- Life expectancy < 3 months
- Severe lung disease (FEV1 < 50% of the normal value)
- Severe psychiatric disorder
- Subjects unlikely to comply with the requirements of the protocol
- Known or current alcohol, medication or drug abuse
- Pregnancy or lactation
- Women of child-bearing potential without reliable contraception
- Participation of the subject in another clinical trial within the last 4 weeks
Location and Contact Information
Germany
Medizinische Klinik und Poliklinik I, University Clinic Carl Gustav Carus, Dresden, 01307, Germany
Platzbecker Uwe, MD, Principal Investigator
Uwe Platzbecker, MD, Principal Investigator, University Clinic Carl Gustav Carus Dresden
More Information
Publications
Antin JH, Kim HT, Cutler C, Ho VT, Lee SJ, Miklos DB, Hochberg EP, Wu CJ, Alyea EP, Soiffer RJ. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003 Sep 1;102(5):1601-5. Epub 2003 May 1.
Barten MJ, Streit F, Boeger M, Dhein S, Tarnok A, Shipkova M, Armstrong VW, Mohr FW, Oellerich M, Gummert JF. Synergistic effects of sirolimus with cyclosporine and tacrolimus: analysis of immunosuppression on lymphocyte proliferation and activation in rat whole blood. Transplantation. 2004 Apr 27;77(8):1154-62. Erratum in: Transplantation. 2005 Jun 27;79(12):1773.
Bornhauser M, Schuler U, Porksen G, Naumann R, Geissler G, Thiede C, Schwerdtfeger R, Ehninger G, Thiede HM. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation. 1999 Feb 27;67(4):499-504.
Cutler C, Kim HT, Hochberg E, Ho V, Alyea E, Lee SJ, Fisher DC, Miklos D, Levin J, Sonis S, Soiffer RJ, Antin JH. Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2004 May;10(5):328-36.
Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA, Starling RC, Sorensen K, Hummel M, Lind JM, Abeywickrama KH, Bernhardt P; RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003 Aug 28;349(9):847-58.
Gratwohl A, Brand R, Apperley J, Biezen Av A, Bandini G, Devergie A, Schattenberg A, Frassoni F, Guglielmi C, Iacobelli S, Michallet M, Kolb HJ, Ruutu T, Niederwieser D; Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (CLWP-EBMT). Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood. 2002 Dec 1;100(12):3877-86.
Hackstein H, Taner T, Zahorchak AF, Morelli AE, Logar AJ, Gessner A, Thomson AW. Rapamycin inhibits IL-4--induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood. 2003 Jun 1;101(11):4457-63. Epub 2003 Jan 16.
Hoyer PF, Ettenger R, Kovarik JM, Webb NJ, Lemire J, Mentser M, Mahan J, Loirat C, Niaudet P, VanDamme-Lombaerts R, Offner G, Wehr S, Moeller V, Mayer H; Everolimus Pediatric Study Group. Everolimus in pediatric de nova renal transplant patients. Transplantation. 2003 Jun 27;75(12):2082-5.
Kovarik JM. Everolimus: a proliferation signal inhibitor targeting primary causes of allograft dysfunction. Drugs Today (Barc). 2004 Feb;40(2):101-9. Review.
Kovarik JM, Kaplan B, Silva HT, Kahan BD, Dantal J, McMahon L, Berthier S, Hsu CH, Rordorf C. Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6 months after kidney transplantation. Am J Transplant. 2003 May;3(5):606-13.
MacDonald AS. Rapamycin in combination with cyclosporine or tacrolimus in liver, pancreas, and kidney transplantation. Transplant Proc. 2003 May;35(3 Suppl):201S-208S. Review.
Monti P, Mercalli A, Leone BE, Valerio DC, Allavena P, Piemonti L. Rapamycin impairs antigen uptake of human dendritic cells. Transplantation. 2003 Jan 15;75(1):137-45.
Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, Przepiorka D, Davies S, Petersen FB, Bartels P, Buell D, Fitzsimmons W, Anasetti C, Storb R, Ratanatharathorn V. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000 Sep 15;96(6):2062-8.
Panwalkar A, Verstovsek S, Giles FJ. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer. 2004 Feb 15;100(4):657-66. Review.
Qi S, Xu D, Peng J, Vu MD, Wu J, Bekersky I, Fitzsimmons WE, Peets J, Sehgal S, Daloze P, Chen H. Effect of tacrolimus (FK506) and sirolimus (rapamycin) mono- and combination therapy in prolongation of renal allograft survival in the monkey. Transplantation. 2000 Apr 15;69(7):1275-83.
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986 Mar 20;314(12):729-35.
Sullivan KM, Anasetti C, Horowitz M, Rowlings PA, Petersdorf EW, Martin PJ, Clift RA, Walters MC, Gooley T, Sierra J, Anderson JE, Bjerke J, Siadak M, Flowers ME, Nash RA, Sanders JE, Appelbaum FR, Storb R, Hansen JA. Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry. Ann N Y Acad Sci. 1998 Jun 30;850:312-24.
Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L, Buckner CD, Anasetti C, Appelbaum FR, Badger C, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989 May 1;73(6):1720-8. Erratum in: Blood 1989 Aug 15;74(3):1180.
Vu MD, Qi S, Xu D, Wu J, Fitzsimmons WE, Sehgal SN, Dumont L, Busque S, Daloze P, Chen H. Tacrolimus (FK506) and sirolimus (rapamycin) in combination are not antagonistic but produce extended graft survival in cardiac transplantation in the rat. Transplantation. 1997 Dec 27;64(12):1853-6.
Woltman AM, van der Kooij SW, Coffer PJ, Offringa R, Daha MR, van Kooten C. Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression. Blood. 2003 Feb 15;101(4):1439-45. Epub 2002 Sep 26.
Xu Q, Simpson SE, Scialla TJ, Bagg A, Carroll M. Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood. 2003 Aug 1;102(3):972-80. Epub 2003 Apr 17.
Record last reviewed: June 2005
Last Updated: July 25, 2005
Record first received: July 7, 2005
ClinicalTrials.gov Identifier: NCT00117702
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices
ClinicalTrials.gov processed this record on 2005-07-26
Resources
- ¿Que es la prueba Pap? (Office of Population Affairs Clearinghouse, OPA, OPHS, OS, HHS)
- ¿Tengo cáncer del cuello del utero? (Office of Population Affairs Clearinghouse, OPA, OPHS, OS, HHS)
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