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

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

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.

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

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