Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Graft Versus Host Disease

This study has been terminated.
(high incidence of TTP, poor recrual)
Sponsor:
Information provided by:
University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT00373815
First received: September 6, 2006
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The present protocol is a dose-finding and toxicity study in preparation of a randomised study comparing current standard treatment CSA/prednisolone with the new combination CSA/prednisolone/everolimus.


Condition Intervention Phase
Graft Versus Host Disease
Drug: Everolimus
Phase 1

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: A Phase I Dose Escalation Study With Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • Feasibility of oral application everolimus
  • Daily dose needed to reach the targeted plasma level everolimus
  • Time to reach the targeted plasma level of everolimus

Secondary Outcome Measures:
  • Incidence and severity of treatment induced toxic events
  • Incidence, severity and seriousness of adverse events
  • Treatment induced morbidity
  • Treatment induced 1-year-mortality
  • Efficacy of everolimus/CSA/prednisolone on aGVHD
  • Drug interactions between everolimus and CSA

Estimated Enrollment: 10
Study Start Date: September 2006
Study Completion Date: October 2009
Detailed Description:

The primary objective of the present study is to evaluate the feasibility of treatment with everolimus in combination with CSA/prednisolone in patients with aGVHD after allogeneic HSCT. This evaluation takes into account the following parameters:

  • Feasibility of oral application everolimus
  • Daily dose needed to reach the targeted plasma level everolimus
  • Time to reach the targeted plasma level of everolimusSecondary objectivesThe study will evaluate the toxicity and safety of the treatment with ever-olimus/CSA/prednisolone with regard to
  • Incidence and severity of treatment induced toxic events
  • Incidence, severity and seriousness of adverse events
  • Treatment induced morbidity
  • Treatment induced 1-year-mortality Furthermore the study will collect data about
  • Efficacy of everolimus/CSA/prednisolone on aGVHD
  • Drug interactions between everolimus and CSA
  Eligibility

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

Inclusion Criteria:

  • Written informed consent prior to inclusion into the study
  • Allogeneic HSCT from HLA-identical related or unrelated donors
  • Clinically confirmed acute GVHD ≥ grade II
  • Age < 70 / > 18 years, male or female
  • Karnofsky performance status > 60 %

Exclusion Criteria:

  • Oral treatment is not feasible
  • Severe hepatic impairment Child-Pugh C
  • Active cerebral epilepsy
  • Renal failure (Creatinine clearance < 50 ml/min)
  • Life expectancy < 3 months
  • Known hypersensitivity to everolimus, sirolimus or to any of the excipients
  • Confirmed pregnancy (serum β-HCG)
  • Non-effective contraception for both, male and female patients, if the risk of conception exists
  • Patients with limited legal capacity
  • Patients unwilling and unable to undergo study procedures
  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: NCT00373815

Locations
Germany
Medical Center, Hematology & Oncology, University of Tuebingen
Tuebingen, Germany, D-72076
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
Principal Investigator: Wolfgang A Bethge, MD Medical Center University of Tuebingen
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00373815     History of Changes
Other Study ID Numbers: 2006-002577-44
Study First Received: September 6, 2006
Last Updated: May 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Tuebingen:
acute GVHD
Immunosuppression

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Cyclosporins
Cyclosporine
Everolimus
Sirolimus
Prednisolone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on September 18, 2014