Single-centre Study of Everolimus as GvHD Prophylaxis After Post-Transplantation Cyclophosphamide After Allogeneic SCT

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Single-centre Study of Certican (Everolimus) as Prophylaxis for Graft-versus-Host Disease Following Post-Transplantation Cyclophosphamide After Allogeneic 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: 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

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus as part of GvHD prophylaxis after allogeneic SCT<br>Everolimus from day +5 to day +100 | Drug: Everolimus<br>* GvHD prophylaxis<br>* Other names: Certican;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute GvHD III-IV° until day +100 after allogenic stem cell transplantation | GvHD | day 100 after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute GvHD II-IV° until day +100 after allogenic stem cell transplantation | GvHD | day 100 after transplantation | 
| Incidence of severe chronic GvHD | cGvHD | 720 days after transplantation | 
| Incidence of overall chronic GvHD | cGvHD | 720 days after transplantation | 
| Relapse incidence | Relapse | 720 days after transplantation | 
| Non-relapse mortality | NRM | 720 days after transplantation | 
| Overall survival | OS | 720 days after transplantation | 
| Immune reconstitution | Number of CD3, CD4, CD8, CD20 and CD56 positive cells in peripheral blood | day 100 after transplantation | 
| Engraftment | absolute neutrophil count > 500/ul and platelet count > 50.000/ul | day 100 after transplantation | 
| Chimerism | % donor cells in peripheral blood or bone marrow | day 100 after transplantation |