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

June 17, 2009 updated by: Technische Universität Dresden

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Dresden, Germany, 01307
        • Medizinische Klinik und Poliklinik I, University Clinic Carl Gustav Carus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Technische Universität Dresden

Investigators

  • Principal Investigator: Uwe Platzbecker, MD, University Clinic Carl Gustav Carus Dresden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

June 30, 2005

First Submitted That Met QC Criteria

June 30, 2005

First Posted (Estimate)

July 8, 2005

Study Record Updates

Last Update Posted (Estimate)

June 18, 2009

Last Update Submitted That Met QC Criteria

June 17, 2009

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 30 (AIFA)
  • 2005-000161-19 (EudraCT Nr.)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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