Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Graft Versus Host Disease
Primary Purpose
Graft Versus Host Disease
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease focused on measuring acute GVHD, Immunosuppression
Eligibility 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
Sites / Locations
- Medical Center, Hematology & Oncology, University of Tuebingen
Outcomes
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
Full Information
NCT ID
NCT00373815
First Posted
September 6, 2006
Last Updated
May 28, 2014
Sponsor
University Hospital Tuebingen
1. Study Identification
Unique Protocol Identification Number
NCT00373815
Brief Title
Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Graft Versus Host Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Terminated
Why Stopped
high incidence of TTP, poor recrual
Study Start Date
September 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
University Hospital Tuebingen
4. Oversight
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease
Keywords
acute GVHD, Immunosuppression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Everolimus
Primary Outcome Measure Information:
Title
Feasibility of oral application everolimus
Title
Daily dose needed to reach the targeted plasma level everolimus
Title
Time to reach the targeted plasma level of everolimus
Secondary Outcome Measure Information:
Title
Incidence and severity of treatment induced toxic events
Title
Incidence, severity and seriousness of adverse events
Title
Treatment induced morbidity
Title
Treatment induced 1-year-mortality
Title
Efficacy of everolimus/CSA/prednisolone on aGVHD
Title
Drug interactions between everolimus and CSA
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang A Bethge, MD
Organizational Affiliation
Medical Center University of Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Center, Hematology & Oncology, University of Tuebingen
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
12. IPD Sharing Statement
Links:
URL
http://www.onkologie-tuebingen.de
Description
Related Info
Learn more about this trial
Everolimus in Combination With Cyclosporine A and Prednisolone for the Treatment of Graft Versus Host Disease
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