chronic Graft versus Host Disease MedDRA version: 14.1 Level: LLT Classification code 10018799 Term: GVHD System Organ Class: 10021428 - Immune system disorders MedDRA version: 14.1 Level: LLT Classification code 10063109 Term: Transfusion associated GVHD System Organ Class: 10021428 - Immune system disorders MedDRA version: 14.1 Level: LLT Classification code 10068907 Term: CGVHD System Organ Class: 10021428 - Immune system disorders MedDRA version: 14.1 Level: LLT Classification code 10018
Conditions
Interventions
Trade Name: Certican
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive na
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Diagnosis of classic chronic GvHD according to NIH criteria [33] and fulfilment of criteria for moderate or severe cGvHD •Diagnosis of overlap syndrome according to NIH criteria [33] and fulfilment of criteria for moderate or severe cGvHD and = clinical grade 2 of acute GvHD of the gut and no grade 4 acute GvHD of the skin. NB: A maximum of 30 Patients with overlap syndrome will be included in the trial. •Less than 72 hours after initiation of systemic treatment for cGVHD •Age = 18 years •Patient’s written informed consent •Women and men capable of reproduction must agree to use adequate contraceptive measures (condom, intrauterine devices, oral contraceptives) until three months after termination of treatment 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: •Late persistent or recurrent acute GvHD without evidence of cGvHD •Relapsed or progressive malignant disease (other than minimal residual disease diagnosed by molecular methods) •Severe uncontrolled infections •Pregnant or lactating women •Inabilty to tolerate 1 mg/kg prednisone •Inability to take oral medication •Known hypersensitivity to everolimus •History of mTOR-inhibitor associated non-infectious pneumonitis •Participation in another interventional clinical trial with intervention within 72h •Psychiatric illness that would prevent granting of informed consent •Active viral infection with HIV, hepatitis B or hepatitis C •Severe cardiovascular disease (uncontrolled arrhythmias, congestive heart failure NYHA III or IV, or symptomatic ischemic heart disease) •History of mTOR-inhibitor or CNI-associated TMA that led to discontinuation of mTOR-inhibitor or CNI •Patients with neutrophils < 1000 /µl and / or requiring platelet transfusions at time of screening •Donor lymphocyte infusion with the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to investigate the clinical benefit of treatment with prednisone and everolimus in patients with chronic GVHD.;Secondary Objective: survival rate, time to response, time to treatment failure, relapse rate of underlying malignancies, safety;Primary end point(s): The primary endpoint is the rate of treatment success at 6 months after initiation of treatment for chronic GvHD. Treatment success is defined as: Patient being alive and having achieved a CR or PR of cGvHD without addition of secondary systemic treatment for cGvHD (see below) and with no development of relapse of underlying disease. Addition of any immunosuppressive or immunomodulatory systemic therapy aimed at treating or controlling symptoms of chronic GvHD is considered treatment failure. Examples of secondary systemic therapies include (but are not limited to) cyclosporine A, tacrolimus, methotrexate, mycophenolate, rituximab, azathioprine, pentostatine, cyclophosphamid, chloroquine, imatinib, dasatinib, thalidomide, alemtuzumab, etanercept, antithymocyteglobuline, infliximab, basiliximab, daclizumab, extracorporeal photopheresis, psoralen with UVA-irradiation (PUVA), pulsed steroid exceeding a dose of 2mg/kg/day. ;Timepoint(s) of evaluation of this end point: month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •To evaluate the overall survival rate of patients treated with prednisone and everolimus for chronic GvHD •To evaluate the speed of response (time to achievement of CR or PR) of patients treated with prednisone and everolimus for chronic GvHD. •To evaluate the time to treatment failure, treatment failure being defined as progression of cGvHD after = 2 weeks in any organ, lack of response (CR/PR) after 14 weeks and/or addition of secondary systemic treatment for cGvHD. •To evaluate the relapse rate of underlying malignancies of patients treated with prednisone and everolimus for chronic GvHD •To assess the side effects of prednisone and everolimus in patients with chronic GvHD (see safety endpoints below) ;Timepoint(s) of evaluation of this end point: end of trial | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
University Medical Center Hamburg-Eppendorf
Outcome results
None listed