Tocilizumab for Chronic Graft-versus-Host Disease Treatment
- Conditions
- Graft Versus Host Disease
- Interventions
- Biological: tocilizumabOther: laboratory biomarker analysisOther: quality-of-life assessment
- Registration Number
- NCT02174263
- Lead Sponsor
- Fred Hutchinson Cancer 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.
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Supportive care (tocilizumab) 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). Supportive care (tocilizumab) laboratory biomarker analysis 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). Supportive care (tocilizumab) quality-of-life assessment 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).
- Primary Outcome Measures
Name Time Method FFS At 6 months
- Secondary Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (5)
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States