Tocilizumab for Chronic Graft-versus-Host Disease Treatment

This is an interventional supportive care trial for Graft Versus Host Disease Read More

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