Trial Information

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

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 weekly 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 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 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 replaced on study. Follow-up data will be required unless consent for data collection is
withdrawn:

- Additional systemic GVHD therapy is added for disease progression or non-response

- Steroid dose is escalated to ≥ 2.5 mg/kg/day of prednisone (or methylprednisolone
equivalent of 2 mg/kg/day) for GVHD progression or no response

- Development of toxicity that requires withholding of study medication for more then 14
days