Tocilizumab in Chronic GVHD Refractory to at Least Two Prior Therapies
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 5
- 主要终点
- FFS
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: laboratory biomarker analysis (Other)
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).
干预措施: quality-of-life assessment (Other)
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).
干预措施: tocilizumab (Biological)
结局指标
主要结局
FFS
时间窗: At 6 months
次要结局
- 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)