Clinical trial NCT00373815: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Graft Versus Host Disease
Keywords: acute GVHD
Immunosuppression
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2006-09-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Feasibility of oral application everolimus
measure: Daily dose needed to reach the targeted plasma level everolimus
measure: Time to reach the targeted plasma level of everolimus
Secondary outcomes:
measure: Incidence and severity of treatment induced toxic events
measure: Incidence, severity and seriousness of adverse events
measure: Treatment induced morbidity
measure: Treatment induced 1-year-mortality
measure: Efficacy of everolimus/CSA/prednisolone on aGVHD
measure: Drug interactions between everolimus and CSA
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: Medical Center, Hematology & Oncology, University of Tuebingen
Study officials:
affiliation: Medical Center University of Tuebingen
name: Wolfgang A Bethge, MD
role: PRINCIPAL_INVESTIGATOR
References: