Phase II open-label pilot study evaluating the safety and efficacy of Certican ® (everolimus) in the prevention of chronic graft-versus-host disease and late pulmonary complications after allogeneic hematopoietic stem cell transplantation blood - GMIHO-004/2006

Phase 1

• Conditions: Prevention of chronic graft-versus-host disease and late pulmonary complications after allogeneic hematopoietic stem cell transplantation blood; MedDRA version: 14.0Level: PTClassification code 10053239Term: Prophylaxis against graft versus host diseaseSystem Organ Class: 10042613 - Surgical and medical procedures

• Registration Number: EUCTR2010-023630-24-DE
• Lead Sponsor: GMIHO mbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-03
• Last Update Posted: 10 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• patients after allogeneic blood stem cell transplantation at the age = 18 years
• GvHD prophylaxis with calcineurin inhibitors (cyclosporine A, tacrolimus) and MTX or MMF
(Prior therapy of acute GvHD with additional prednisolone is allowed)
• Increased risk of chronic GvHD, at least one of the following conditions is met:
• Male with female donor
• HLA class I or II mismatch in the GvHD direction
• Continued active acute GvHD on day +50 after transplantation, despite treatment with high dose steroids and cyclosporine A
• Functional one-second-forced vital capacity (FEV1) or diffusion capacity (DLCO) on day +50 after transplantation at least. 25% below the last measured value before transplantation (up to 50 days before transplantation)
• New-onset of acute GvHD between day +50 and +100 after allogeneic blood stem cell transplantation
• Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• use (prophylactic or therapeutic) of mTOR inhibitors after SCT
• Overlap of acute / chronic GvHD
• Total cholesterol = 3 times the upper limit of normal (ULN) or triglycerides = 3 X ULN
• GOT, GPT, bilirubin = 3 times ULN (unless attributable to GvHD)
• creatinine = 3 times ULN
• evidence of active hepatitis B or C
• All of the circumstances in which wound healing may pose a risk, including: surgery in recent weeks, ulcers on the skin or mucous membrane
• Known intolerance to everolimus, sirolimus, or other components of Certican ®
• Lactose intolerance
• Pregnancy or breastfeeding
• Women of childbearing potential except women who meet the following criteria:
• Post-menopausal (12 months natural amenorrhea)
• After surgery (= 6 weeks after bilateral ovariectomy with or without hysterectomy)
• during and at least 6 months after the last dose of everolimus regular and correct use of highly effective contraception (defined as Pearl Index <1) such as birth control pills, hormone IUD, hormonal implants, transdermal patch , a combination of two barrier methods (condom and diaphragm), sexual abstinence
• Men who do not use one of the following options for contraception during at least 6 months after the last dose of everolimus :
• Sexual abstinence
• Condition after vasectomy
• Condom
• restrictions or conditions that affect the ability of a written Informed Consent
• Participation in another interventional study (e.g., for prophylactic immunosuppression in the context of stem cell therapy) within the last 60 days prior to study enrolment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Proportion of patients with early everolimus -<br>Discontinuation of therapy, within 6 weeks beginning<br>treatment with everolimus.<br>The therapy is terminated under the following<br>Conditions:<br>- Unreasonable toxicities<br>- treatment failure, defined as<br>- new onset of chronic GVHD of moderate or strong expression to NIH criteria<br>clearly represents no acute form of GVHD.<br>-deterioration of the LFS to less than 75% of the Baseline value before the start of everolimus therapy<br>- Regulation of an additional immunosuppressive<br>Therapy<br>- secondary endpoint side effects<br>;Main Objective: Frequency of treatment dropout in the first 6<br>Weeks<br>;Secondary Objective: - tolerability of everolimus<br>-frequency and severity of GVHD (graft-versus-host Disease, acc. NIH consensus)and PTOLD (Transplant-associated obstructive Lung disease)<br>- lung function<br>- overall survival after Stammzelltransplantationl<br>