tocilizumab for chronic graft-versus-host disease treatment

Conditions: Graft Versus Host Disease

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.

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.

Eligibility 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