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

This study has been terminated.
(safety reasons)
Sponsor:
Information provided by:
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00117702
First received: June 30, 2005
Last updated: June 17, 2009
Last verified: June 2009

June 30, 2005
June 17, 2009
October 2005
May 2008   (final data collection date for primary outcome measure)
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 ]
Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation
Complete list of historical versions of study NCT00117702 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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
Not Provided
Not Provided
 
Prevention of the Graft-Versus-Host-Disease in Patients After Stem Cell Transplantation With Tacrolimus and Everolimus
Prophylaxis of the Graft-Versus-Host-Disease in Patients After Allogeneic Stem Cell Transplantation With a Combination of 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.

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.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Graft vs Host Disease
  • Drug: Tacrolimus
    day 0-100, then taper
    Other Name: Prograf
  • Drug: Everolimus
    day 0-56
    Other Name: Certican
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
24
May 2008
May 2008   (final data collection date for primary outcome measure)

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 unless they meet the following criteria: postmenopausal (12 months of natural amenorrhea);postoperation status (6 weeks after surgical bilateral oophorectomy with or without hysterectomy);use of highly effective birth control method (defined as one which results in a low failure rate i.e. less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomized partner)
  • Men that do not use one of the following methods for prevention of conception:sexual abstinence; condom; vasectomy
  • Participation of the subject in another clinical trial within the last 4 weeks
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00117702
30, 2005-000161-19 (EudraCT Nr.)
Yes
TUD, Technical University Dresden
Technische Universität Dresden
Not Provided
Principal Investigator: Uwe Platzbecker, MD University Clinic Carl Gustav Carus Dresden
Technische Universität Dresden
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP