Tocilizumab for Chronic Graft-versus-Host Disease Treatment
Study Details
Study Description
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 |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- Efficacy will be determined by the proportion of patients with failure free survival (FFS) at 6 months.
SECONDARY OBJECTIVES:
-
Patients achieving a complete response (CR) or partial response (PR) at 6 months based on clinician judged response.
-
Patients achieving a CR or PR by objective response measures at 6 months.
-
Failure-free survival (FFS) at 1 year.
-
Change in steroid dose from enrollment to 6 months (mo).
TERTIARY OBJECTIVES:
- 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.
Study Design
Arms and Interventions
| 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:
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- FFS [At 6 months]
Secondary Outcome Measures
- 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]
Prednisone is not a pre-specified intervention; however, some patients may take prednisone while on this study.
Other Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
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Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
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Subject underwent allogeneic stem cell transplantation at least 6 months prior to enrollment
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Subject has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
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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
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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
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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
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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
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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
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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
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Immunization with a live, attenuated vaccine within 4 weeks prior to study enrollment
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History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
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Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
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Pregnant or breast-feeding women
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Patients (both men and women) with reproductive potential not willing to use an effective method of contraception
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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)
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Total bilirubin > upper limit of normal (ULN)
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Absolute neutrophil count < 1.5 x 109/L (1500/mm3)
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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
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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
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History of diverticulitis, Crohn's disease or ulcerative colitis
-
History of demyelinating disorder
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Hospital | Phoenix | Arizona | United States | 85054 |
| 2 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 3 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 4 | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
| 5 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Stephanie Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 9130
- NCI-2014-01204
- 9130
- P30CA015704