Clinical Trial: Prevention of the Graft-Versus-Host-Disease in Patients After Stem Cell Transplantation With Tacrolimus and Everolimus

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Prophylaxis of the Graft-Versus-Host-Disease in Patients After Allogeneic Stem Cell Transplantation With a Combination of Tacrolimus and Everolimus

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Technische Universität Dresden

Current Primary Outcome: Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation [ Time Frame: first 100 days ]

Original Primary Outcome: Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation

Current Secondary Outcome:

  • Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0) [ Time Frame: within 100 days after Tx ]
  • Hypersensitivity reactions [ Time Frame: within 56 days after Tx ]
  • Thrombotic thrombocytopenic purpura [ Time Frame: within 56 days after Tx ]
  • Hyperlipidemia [ Time Frame: within 56 days after Tx ]
  • Total and relapse-free survival rate one year after the stem cell transplantation


Original Secondary Outcome:

  • 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


Information By: Technische Universität Dresden

Dates:
Date Received: June 30, 2005
Date Started: October 2005
Date Completion:
Last Updated: June 17, 2009
Last Verified: June 2009