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Tocilizumab for Chronic Graft-versus-Host Disease Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02174263
Recruitment Status : Withdrawn (Study never opened due to lack of funds.)
First Posted : June 25, 2014
Last Update Posted : May 6, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Biological: tocilizumab Other: laboratory biomarker analysis Other: quality-of-life assessment Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Efficacy will be determined by the proportion of patients with failure free survival (FFS) at 6 months.

SECONDARY OBJECTIVES:

I. Patients achieving a complete response (CR) or partial response (PR) at 6 months based on clinician judged response.

II. Patients achieving a CR or PR by objective response measures at 6 months.

III. Failure-free survival (FFS) at 1 year.

IV. Change in steroid dose from enrollment to 6 months (mo).

TERTIARY OBJECTIVES:

I. Biologic studies will be done to determine possible mechanisms of response.

OUTLINE:

Patients receive tocilizumab intravenously (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).

After completion of study treatment, patients are followed up at 3 and 6 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Tocilizumab in Chronic GVHD Refractory to at Least Two Prior Therapies
Study Start Date : February 2016
Estimated Primary Completion Date : August 2019


Arm Intervention/treatment
Experimental: Supportive care (tocilizumab)
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: tocilizumab
Given IV
Other Names:
  • 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

Other: laboratory biomarker analysis
Correlative studies

Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment




Primary Outcome Measures :
  1. FFS [ Time Frame: At 6 months ]

Secondary Outcome Measures :
  1. Patients achieving CR or PR based on objective measures, as recommended by the NIH Consensus Conference for chronic GVHD [ Time Frame: At 6 months ]
  2. Patients achieving a CR or PR based on clinician judged response [ Time Frame: At 6 months ]
  3. Relative change in daily prednisone dose [ Time Frame: Baseline to 6 months ]
    Prednisone is not a pre-specified intervention; however, some patients may take prednisone while on this study.


Other Outcome Measures:
  1. B cell subsets [ Time Frame: Up to week 21 ]
  2. Tumor necrosis factor (ligand) superfamily, member 13b (BAFF) levels [ Time Frame: Up to week 21 ]
  3. T cell subsets [ Time Frame: Up to week 21 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Known uncontrolled cytomegalovirus (CMV) polymerase chain reaction (PCR) reactivation per institutional standards; once CMV has been treated and stable per institutional standards, patient may be enrolled; CMV PCR will be tested within two weeks prior to starting study drug
  • History of diverticulitis, Crohn's disease or ulcerative colitis
  • History of demyelinating disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02174263


Locations
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United States, Arizona
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephanie Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02174263    
Other Study ID Numbers: 9130
NCI-2014-01204 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9130 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: June 25, 2014    Key Record Dates
Last Update Posted: May 6, 2016
Last Verified: May 2016
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Immunoglobulins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs