NCT02174263

Brief Summary

This phase II trial studies how well tocilizumab works in treating chronic graft-versus-host disease (GVHD) in patients that have not responded to treatment after at least two prior therapies. Tocilizumab blocks a protein that stimulates the body's immune system. By blocking this protein, the investigators may reduce the symptoms of chronic GVHD.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

5 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 23, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 25, 2014

Completed
1.6 years until next milestone

Study Start

First participant enrolled

February 1, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2019

Completed
Last Updated

May 6, 2016

Status Verified

May 1, 2016

Enrollment Period

3.5 years

First QC Date

June 23, 2014

Last Update Submit

May 5, 2016

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

  • FFS

    At 6 months

Secondary Outcomes (3)

  • Patients achieving CR or PR based on objective measures, as recommended by the NIH Consensus Conference for chronic GVHD

    At 6 months

  • Patients achieving a CR or PR based on clinician judged response

    At 6 months

  • Relative change in daily prednisone dose

    Baseline to 6 months

Other Outcomes (3)

  • B cell subsets

    Up to week 21

  • Tumor necrosis factor (ligand) superfamily, member 13b (BAFF) levels

    Up to week 21

  • T cell subsets

    Up to week 21

Study Arms (1)

Supportive care (tocilizumab)

EXPERIMENTAL

Patients receive tocilizumab IV over 1 hour every 2 weeks for 12 weeks (weeks 1, 3, 5, 7, 9, and 11) and then every 4 weeks for 12 weeks (weeks 13, 17, and 21).

Biological: tocilizumabOther: laboratory biomarker analysisOther: quality-of-life assessment

Interventions

tocilizumabBIOLOGICAL

Given IV

Also known as: Actemra, immunoglobulin G1, anti-(human interleukin 6 receptor) (human-mouse monoclonal MRA heavy chain), disulfide with human-mouse monoclonal MRA kappa chain dimer, MRA, R-1569, RoActemra
Supportive care (tocilizumab)
laboratory biomarker analysisOTHER

Correlative studies

Supportive care (tocilizumab)
quality-of-life assessmentOTHER

Ancillary studies

Also known as: quality of life assessment
Supportive care (tocilizumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
  • Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
  • Subject underwent allogeneic stem cell transplantation at least 6 months prior to enrollment
  • Subject has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
  • Female subjects of child bearing potential must have a negative pregnancy test prior to first dose of tocilizumab and must agree to practice effective contraception during the study
  • Subject meets the following medication restriction requirements and agrees to follow medication restrictions during the study; the following concomitant medications are not allowed: cyclophosphamide, abatacept, etanercept, adalimumab infliximab, golimumab, tofacitinib, and alemtuzumab; these medications also cannot have been used for 5 half-lives prior to enrollment
  • Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits

You may not qualify if:

  • Donor lymphocyte infusion in the preceding 100 days
  • Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
  • Uncontrolled bacterial, viral infection or invasive fungal infection
  • Evidence of malignancy within 6 months of study enrollment; this is defined as clear morphologic, radiologic or molecular evidence of disease; mixed chimerism is allowed at the discretion of the clinician
  • Treatment with any non-Food and Drug Administration (FDA) approved agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of study enrollment
  • Immunization with a live, attenuated vaccine within 4 weeks prior to study enrollment
  • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
  • Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
  • Pregnant or breast-feeding women
  • Patients (both men and women) with reproductive potential not willing to use an effective method of contraception
  • Serum creatinine \> 1.6 mg/dL (141 umol/L) in females and \> 1.9 mg/dL (168 umol/L) in males; patients with serum creatinine values exceeding these limits are eligible for the study if their estimated glomerular filtration rates (GFR) are \> 30 ml/min/1.73 m\^2
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times upper limit of normal (ULN)
  • Total bilirubin \> upper limit of normal (ULN)
  • Absolute neutrophil count \< 1.5 x 10\^9/L (1500/mm\^3)
  • Known active hepatitis B or C; patients must have a negative test for hepatitis B surface antigen, hepatitis B core antibody and hepatitis C antibody within 4 weeks prior to starting study drug
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

tocilizumabImmunoglobulin GDisulfides

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSulfidesAnionsIonsElectrolytesInorganic ChemicalsHydrogen SulfideSulfur CompoundsOrganic Chemicals

Study Officials

  • Stephanie Lee

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 23, 2014

First Posted

June 25, 2014

Study Start

February 1, 2016

Primary Completion

August 1, 2019

Last Updated

May 6, 2016

Record last verified: 2016-05

Locations

US(5)