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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Everolimus|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute GVHD, Immunosuppression