Prevention of the Graft-Versus-Host-Disease in Patients After Stem Cell Transplantation With Tacrolimus and Everolimus
The purpose of this pilot study is to provide preliminary data about the efficacy and the safety of the combination of tacrolimus with everolimus in the prophylaxis of the graft-versus-host-disease (GvHD) in patients after allogeneic stem cell transplantation.
Graft vs Host Disease
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prophylaxis of the Graft-Versus-Host-Disease in Patients After Allogeneic Stem Cell Transplantation With a Combination of Tacrolimus and Everolimus|
- Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation [ Time Frame: first 100 days ] [ Designated as safety issue: Yes ]
- Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0) [ Time Frame: within 100 days after Tx ] [ Designated as safety issue: Yes ]
- Hypersensitivity reactions [ Time Frame: within 56 days after Tx ] [ Designated as safety issue: Yes ]
- Thrombotic thrombocytopenic purpura [ Time Frame: within 56 days after Tx ] [ Designated as safety issue: Yes ]
- Hyperlipidemia [ Time Frame: within 56 days after Tx ] [ Designated as safety issue: Yes ]
- Total and relapse-free survival rate one year after the stem cell transplantation [ Designated as safety issue: No ]
|Study Start Date:||October 2005|
|Study Completion Date:||May 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
The allogeneic stem cell transplantation is a successful therapeutic approach in the treatment of a number of hematologic diseases. Nevertheless, it is associated with substantial risks and complications. A major life-threatening complication that occurs in the post transplantation period is the graft versus host disease, especially its severe forms (Grade III and Grade IV). For this reason, a combined immunosuppressive therapy is standard in patients after a stem cell transplantation. In this regard, the combination between cyclosporin A and methotrexate in the prevention of GvHD has been particularly successful. However, the incidence rate of GvHD and consequent mortality are still fairly high. Besides, the therapy itself is accompanied by serious side effects. Therefore, there is a need for a more efficient, less toxic, combined immunosuppressive therapy. The purpose of this pilot study is to test a new combination of immunosuppressives (tacrolimus and everolimus) for the prevention of GvHD after an allogeneic stem cell transplantation. Tacrolimus is a macrolide immunosuppressant that acts as a calcineurin inhibitor, thereby preventing the activation and proliferation of the T-lymphocytes. Everolimus is a semisynthetic macrocyclic lactone that inhibits the activity of a key protein involved in the regulation of the cell cycle, the so called m-TOR protein. Both medicaments act complementary and potently inhibit the proliferation of immune cells. Previous studies have shown that the combination of tacrolimus with everolimus decreases significantly the rejection rate after solid organ transplantation and this combination is generally well tolerated.
This study is designed as a prospective, single-center, non-randomized, open-label non-controlled pilot study. Study related visits are scheduled to take place at regular time intervals and the patients will be followed up to one year after the stem cell transplantation. The study is designed and will be conducted in accordance with the ICH-GCP guidelines and the respective national and international laws.
|Medizinische Klinik und Poliklinik I, University Clinic Carl Gustav Carus|
|Dresden, Germany, 01307|
|Principal Investigator:||Uwe Platzbecker, MD||University Clinic Carl Gustav Carus Dresden|