Graft Versus Host Disease
Conditions
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.
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.
Interventions
BIOLOGICALtocilizumab
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
OTHERquality-of-life assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| FFS | At 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Tumor necrosis factor (ligand) superfamily, member 13b (BAFF) levels | Up to week 21 |
| T cell subsets | Up to week 21 |
| B cell subsets | Up to week 21 |
Countries
United States
Outcome results
None listed