Randomized, Placebo-Controlled, Phase II Trial Examining Ustekinumab for Prevention of Graft Vs. Host Disease After Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 116
- 试验地点
- 4
- 主要终点
- Grade II-IV acute graft versus host disease (GVHD) survival
研究概览
简要总结
This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant. Sometimes the transplanted cells from a donor can attack the body's normal tissues (called graft-versus-host disease). Giving ustekinumab after the transplant may help prevent acute graft-versus-host disease by controlling the body's immune response. Funding Source- FDA OOPD.
详细描述
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab intravenously (IV). Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab subcutaneously (SC) on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
ARM II: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence grade III-IV acute GVHD, of disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
After completion of study, patients are followed up at 6, 9, 12, 18, and 24 months post-HCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 - 70
- •Signed informed consent.
- •Hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation
- •Adequate vital organ function:
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% of predicted values on pulmonary function tests
- •Transaminases (aspartate aminotransferase [AST], aspartate aminotransferase [ALT]) < 3 times upper limit of normal values
- •Creatinine clearance ≥ 50 cc/min.
- •Performance status: Karnofsky Performance Status Score ≥ 70%.
- •HCT donor is at least 8/8 (matched at HLA-A, -B, -C, -DRB1) matched with the recipient
- •PBSC (peripheral blood mobilized stem cells) as graft source
- •Fully myeloablative, reduced-toxicity ablative, or reduced-intensity conditioning regimens. If melphalan is part of the conditioning regimen, dose must be at least 75mg/m^2
排除标准
- •Active infection not controlled with appropriate antimicrobial therapy
- •Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
- •Anti-thymocyte globulin (ATG) as part of the conditioning regimen or GVHD prophylaxis
- •Pregnant or nursing women
- •Subjects of childbearing age unwilling to use an effective birth control method or refrain from sexual intercourse until 15 weeks after last dose of study drug
- •Non-myeloablative conditioning regimens or conditioning regimens that use less than 75mg/m^2 of melphalan
- •Prior allogeneic transplant
- •Non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia)
- •Positive screening test for tuberculosis
研究组 & 干预措施
Arm II (placebo)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Questionnaire Administration (Other)
Arm I (ustekinumab)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Quality-of-Life Assessment (Other)
Arm I (ustekinumab)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Questionnaire Administration (Other)
Arm I (ustekinumab)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Ustekinumab (Biological)
Arm II (placebo)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Placebo Administration (Drug)
Arm II (placebo)
Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Grade II-IV acute graft versus host disease (GVHD) survival
时间窗: At 6 months post-hematopoietic cell transplantation (HCT)
Will be treated as a binary outcome, and the Cochran-Mantel-Haenszel test will be used to compare the two groups based on the stratification factors.
次要结局
- Cumulative incidence of grade II-IV and grade III-IV acute GVHD(At 6 months post-HCT)
- Incidence of overall chronic GVHD(From time of HCT, assessed up to 2 years post-HCT)
- Acute GVHD organ staging, overall grading, and classification(From time of HCT, assessed up to day 100 post-HCT)
- Incidence of post-HCT relapse(From time of HCT, assessed up to 2 years post-HCT)
- Incidence of moderate-severe chronic GVHD(From time of HCT, assessed up to 2 years post-HCT)
- Incidence of non-relapse mortality(From time of HCT, assessed up to 2 years post-HCT)
- Relapse-free survival(From time of HCT, assessed up to 2 years post-HCT)
- Overall survival(From time of HCT, assessed up to 2 years post-HCT)