Clinical Trial: Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase I-II Study Using Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease

Brief Summary: This trial designed to evaluate the toxicity and efficacy of tocilizumab in the treatment of steroid refractory acute Graft versus host disease (GVHD).

Detailed Summary:

Patients who underwent an allogeneic hematopoietic stem cell transplantation, with biopsy proven GVHD, active acute GVHD requiring systemic immune suppressive therapy and that failed or did not respond to first line of therapy (corticosteroids ± other agent).

Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks. Subsequent discontinuation of Tocilizumab will occur once patients are off other immune suppressive medications (including extracorporeal photopheresis, ECP) or are receiving sub therapeutic levels of immunosuppression (ie. FK levels <5ng/mL) or prednisone dose <20mg/day (or equivalent) and are free of acute GVHD signs or symptoms for at least one month.

Patients who fulfill criteria of progression of GVHD not in the setting of immunosuppressive taper, no response of GVHD or require initiation of other immune suppressive treatment for GVHD will have Tocilizumab discontinued.

Tocilizumab shall be discontinued and not re-instituted if any one of the following criteria is met. The patient will be taken off study drug therapy at that point, but still followed for primary and secondary study endpoints. A response assessment will be made at the time of therapy discontinuation and at subsequent defined study endpoints. The patient will not be
Sponsor: Medical College of Wisconsin

Current Primary Outcome: The primary objective of the study is to determine the response rate (complete and partial) at day 56 after administration of Tocilizumab for treatment of steroid refractory GVHD [ Time Frame: Day 56 ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Proportion of patients with partial, mixed or no GVHD responses [ Time Frame: 1 year ]

Also measure GVHD progression, primary treatment failures, GVHD flares, discontinuation of immunosuppression, incidence of chronic GVHD, overall survival, incidence of toxicities and infections. For patients with malignant disease, disease-free survival and non-relapse mortality.


Original Secondary Outcome: Same as current

Information By: Medical College of Wisconsin

Dates:
Date Received: November 16, 2011
Date Started: August 2011
Date Completion: August 2021
Last Updated: February 17, 2016
Last Verified: February 2016