A phase II clinical study to assess the efficacy of short-term everolimus as prophylaxis for Graft-versus-Host disease (GvHD) in addition to post-transplantation cyclophosphamide after allogeneic hematopoietic stem cell transplantation in patients with haematological malignancies

Title of the clinical study: A single-centre study of Certican (everolimus) as Prophylaxis for Graft-versus-Host Disease following Post-Transplantation Cyclophosphamide after Allogeneic Stem Cell Transplantation (OCTET-EVER)

Indication: Patients with haematological malignancies after allogeneic haematopoietic stem cell transplantation with a matched related or unrelated donor following reduced intensity conditioning and post-transplantation cyclophosphamide

Phase: Phase II clinical study

Type of study, study design, methodology: Single centre single arm clinical trial, A'Hern's single stage phase II procedure

Number of subjects: 20 (17 total evaluable)

Primary study objective To assess the efficacy of short-term everolimus as GvHD prophylaxis in addition to post-transplantation cyclophosphamide after allogeneic hematopoietic stem cell transplantation in patients with haematological malignancies and to describe the influence of the modified immunosuppression concept on the incidence and severity of acute GvHD, relapse rates, minimal residual disease, immune reconstitution and chimerism.

Medical condition or disease to be investigated:

• Patients with haematological malignancies after allogeneic haematopoietic stem cell transplantation with a matched related or unrelated donor following reduced intensity conditioning and post-transplantation cyclophosphamide

Name of investigational medicinal product (IMP): Everolimus (Certican®) Investigational medicinal product - dosage and method of administration: 1,5mg per os twice a day (target blood level 5 to 10ng/ml) from day +5 to day +100 after allogeneic stem cell transplantation

Duration of treatment: The treatment will be given from day +5 to day +100 after allogeneic stem cell transplantation. The observation time will last from day +5 to day +130. Incidence of chronic GvHD, overall survival and relapse incidence will be recorded on d+365 and d+720 after transplant.

Inclusion Criteria:

• Patients with haematological malignancies after allogeneic haematopoietic stem cell transplantation with a matched related or unrelated donor following reduced intensity conditioning and post-transplantation cyclophosphamide

Principal inclusion criteria:

• Written informed consent

Exclusion Criteria:

• Known intolerance to everolimus
• Presence or history of Microangiopathy
• Presence of uncontrolled infections
• Severe organ dysfunction defined as:
• Cardiac left ventricular ejection fraction (LVEF) of less than 35%
• Diffusing lung capacity (DLCO) of less than 40%
• Total lung capacity (TLC) of less than 40%
• Forced expiratory volume (FEV1) of less than 40%
• Total bilirubin >3mg/dl
• Creatinine-clearance of less than 40 ml/min
• Pregnancy or breast feeding
• Participation in other experimental drug trials