Treatment of Newly Diagnosed Moderate or Severe Chronic Graft-versus-host Disease With Prednisone and Everolimus

NCT01862965 | Completed Phase 2 DMC

• 2 other identifiers: PredEver first2011-004847-35
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

In this study patients with moderate to severe chronic graft-versus-host disease will be treated with a combination of prednisone and everolimus. Patients will be treated on the study for a maximum of 12 months and followed up for another 12 months. The primary hypothesis of this study is that the addition of everolimus to prednisone increases response rates without increasing treatment related mortality or mortality due to relapse of underlying disease.

Conditions

Chronic Graft-versus-host Disease

Keywords

firstline; treatment; prednisone; everolimus

Outcome Measures

Primary Outcomes (1)

• rate of treatment success

  Patient being alive and having achieved a CR or PR of cGvHD without addition of secondary systemic treatment for cGvHD (see below) and without development of relapse of underlying disease. Addition of any immunosuppressive or immunomodulatory systemic therapy aimed at treating or controlling symptoms of chronic GvHDcGvHD is considered treatment failure. Examples of secondary systemic therapies include (but are not limited to) cyclosporine ACSA, tacrolimus, methotrexate, mycophenolate, rituximab, azathioprine, pentostatine, cyclophosphamid, chloroquine, imatinib, dasatinib, thalidomide, alemtuzumab, etanercept, antithymocyte globulin, infliximab, basiliximab, daclizumab, extracorporeal photopheresis, psoralen with UVA-irradiation (PUVA), pulsed steroid exceeding a dose of 2 mg/kg/day.

  at 6 months

Secondary Outcomes (5)

• the overall survival rate of patients treated with prednisone and everolimus for chronic GvHDcGvHD

  1 year

• time to treatment failure

  average time up to 12 months from start of treatment

• speed of response

  average time up to 12 months from start of treatment

• Relapse of underlying disease

  1 year

• side effects

  1 year

Other Outcomes (1)

• Safety endpoints

  1 year

Study Arms (1)

PredEver

EXPERIMENTAL

Prednisone and Everolimus

Drug: PredEver

Interventions

PredEver DRUG

Firstline treatment with prednisone and Everolimus

PredEver

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥ 18 years
• Diagnosis of classic chronic GvHDcGvHD according to NIH criteria \[33\] and fulfilment of criteria for moderate or severe cGvHD or o 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.

You may not qualify if:

• 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
• Inability 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 \< 30 days
• Prior use of mTOR- inhibitor (everolimus or sirolimus) for treatment of acute GvHD
• Prior systemic treatment for chronic GvHD\>of cGvHD ≥ 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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Novartis: collaborator
• Crolll Gmbh: collaborator

Study Sites (6)

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07743, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55101, Germany

Location

Klinikum der Universität Regensburg

Regensburg, 93053, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Deutsche Klinik fuer Diagnostik GmbH

Wiesbaden, 65191, Germany

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 27, 2013
• Study Start: March 6, 2013
• Primary Completion: February 7, 2018
• Study Completion: March 1, 2019
• Last Updated: April 2, 2020

Record last verified: 2020-04

Locations

DE (6)