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

This study is currently recruiting participants.
Verified January 2014 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
William R. Drobyski, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01475162
First received: November 16, 2011
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Acute Graft Versus Host Disease
Drug: Tocilizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I-II Study Using Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with partial, mixed or no GVHD responses [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 21
Study Start Date: August 2011
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab

Drug: Tocilizumab

Other Names:

Actemra

Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.

Drug: Tocilizumab
Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.
Other Name: Actemra

Detailed Description:

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 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01475162

Contacts
Contact: William R Drobyski, MD 414-456-4941 wdrobysk@mcw.edu
Contact: Barbara M Davies, BS 414-805-8926 bdavies@mcw.edu

Locations
United States, Wisconsin
Froedtert Hospital/Medical College of Wisconsin-Clinical Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: William R Drobyski, MD    414-456-4941    wdrobysk@mcw.edu   
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: William R Drobyski, MD Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: William R. Drobyski, MD, Professor of Medicine, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01475162     History of Changes
Other Study ID Numbers: MCW-PRO15904
Study First Received: November 16, 2011
Last Updated: January 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
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

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on April 15, 2014