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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Acute Graft Versus Host Disease

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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withdrawn: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


Inclusion Criteria:



- Patients age 18 and older who underwent an allogeneic hematopoietic stem cell
transplantation.

- Patients are required to have biopsy proven GVHD.

- Patients must have active acute GVHD requiring systemic immune suppressive therapy
and that failed or did not respond to first line of therapy.

- First line therapy needs to be a minimum of corticosteroids, methylprednisolone
of 1.6mg/kg/day or prednisone of 2mg/kg/day, alone or combined to other agent.

- Failure of GVHD therapy is defined as flare of signs and symptoms of acute GVHD
or progression of GVHD grade after at least 72 hours from starting therapy.

- No response to GVHD treatment (corticosteroids ± other agent) after a minimum of
7 days of treatment.

- Patient must be able to give informed consent.

Exclusion Criteria:

- Intolerance or allergy to Tocilizumab

- Active uncontrolled infection requiring ongoing treatment with antifungals,
antibiotics or anti-viral drugs.

- Relapsed/persistent malignancy requiring rapid immune suppression withdrawal. Liver
enzymes: ALT and AST > 3x upper limit of normal.

- Patients with severe sinusoidal obstruction syndrome who in the judgement of the
treating physician are not expected to have normalized bilirubin by day 56 after
enrollment.

- Serum bilirubin > 2x upper limit of normal.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Day 56

Safety Issue:

No

Principal Investigator

William R Drobyski, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Medical College of Wisconsin

Authority:

United States: Institutional Review Board

Study ID:

MCW-PRO15904

NCT ID:

NCT01475162

Start Date:

August 2011

Completion Date:

August 2021

Related Keywords:

  • Acute Graft Versus Host Disease
  • acute Graft versus Host Disease (aGVHD)
  • steroid refractory acute Graft versus Host Disease (aGVHD)
  • chronic Graft versus Host Disease (cGVHD)
  • corticosteroids
  • allogeneic hematopoietic stem cell transplantation
  • Graft vs Host Disease

Name

Location

Froedtert Hospital/Medical College of Wisconsin-Clinical Cancer CenterMilwaukee, Wisconsin  53226