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
  Purpose

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.


Condition Intervention Phase
Graft vs Host Disease
Drug: Tacrolimus
Drug: Everolimus
Phase 2
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: October 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tacrolimus
    day 0-100, then taper
    Other Name: Prograf
    Drug: Everolimus
    day 0-56
    Other Name: Certican
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117702

Locations
Germany
Medizinische Klinik und Poliklinik I, University Clinic Carl Gustav Carus
Dresden, Germany, 01307
Sponsors and Collaborators
Technische Universität Dresden
Investigators
Principal Investigator: Uwe Platzbecker, MD University Clinic Carl Gustav Carus Dresden
  More Information

Publications:

Responsible Party: TUD, Technical University Dresden
ClinicalTrials.gov Identifier: NCT00117702     History of Changes
Other Study ID Numbers: 30, 2005-000161-19 (EudraCT Nr.)
Study First Received: June 30, 2005
Last Updated: June 17, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität Dresden:
GvHD
Tacrolimus
Everolimus
Stem cell transplantation

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Everolimus
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 19, 2014