Itacitinib to Prevent Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Graft versus host disease (GVHD)-free/relapse free survival rate
研究概览
简要总结
This phase II trial studies how well itacitinib works in preventing graft versus host disease in patients with blood disorders undergoing donor stem cell transplantation. A donor transplantation uses blood-making cells from a family member or unrelated donor to remove and replace abnormal blood cells. Graft versus host disease is a reaction of the donor's immune cells against the patient's body. Itacitinib plus standard treatment may help prevent graft versus host disease in patients who have received a donor stem cell transplantation.
详细描述
PRIMARY OBJECTIVE:
I. To estimate the graft-versus (vs.) host disease-free/relapse free survival (GRFS) rate of itacitinib used as prophylaxis to prevent graft versus host disease (GVHD) after allogeneic stem cell transplantation (ASCT) at one year.
SECONDARY OBJECTIVES:
I. To assess the time to neutrophil and platelet engraftment and compare between matched and unmatched donors.
II. To assess safety of itacitinib as measured by non-relapse mortality (NRM) at day 100.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Karnofsky performance status of at least 70
- •Patients with hematological disorders undergoing ASCT with conditioning regimen of timed sequential busulfan and fludarabine
- •Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor available
- •Life expectancy of at least 12 weeks (3 months)
- •Direct bilirubin not greater than 1 mg/dL
- •Alanine transaminase (ALT) less than or equal 3 x upper limit of normal range
- •Serum creatinine less than 1.5 x the upper limit of normal range and creatinine clearance greater than 50 ml/min
- •Diffusing capacity for carbon monoxide (DLCO) 65% of predicted corrected for hemoglobin
- •Left ventricle ejection fraction (LVEF) of at least 50%
- •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
- •Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
排除标准
- •Patients with a comorbidity score >
- •The principal investigator is the final arbiter of eligibility and enrollment of patients with comorbidity score > 3 and may permit enrollment of these patients on individual basis
- •Active or clinically significant cardiac disease including:
- •Congestive heart failure New York Heart Association (NYHA) > class II
- •Active coronary artery disease
- •Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
- •Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before transplant, or myocardial infarction within 6 months before transplant
- •Patients with uncontrolled infections
- •Patients with active hepatitis B and C
研究组 & 干预措施
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Busulfan (Drug)
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Fludarabine (Drug)
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Itacitinib (Drug)
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Methotrexate (Drug)
Prevention (itacitinib, busulfan, fludarabine, ASCT)
CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Graft versus host disease (GVHD)-free/relapse free survival rate
时间窗: At 1 year
The proportion of patients who are alive without disease relapse of GVHD at one year will be reported, along with the corresponding 95% confidence interval. Logistic regression will be used to assess the association between success and clinical and treatment covariates of interest.
次要结局
- Incidence of non-relapse mortality(Up to 1 year)
- To assess overall survival and progression-free survival.(From day of transplant until day of death, assessed up to 1 year)
- To assess the toxicity profile associated with this regimen(Up to 1 year)
- To assess the incidence of acute and chronic GVHD.(Up to 1 year)
- Time to neutrophil engraftment(Up to day 42)
- Time to platelet engraftment(Up to day 42)
- To assess the incidence of non-relapse mortality(At day 100)
- Time to disease relapse(Up to 1 year)
- Incidence of withdrawal syndrome in patients with myelofibrosis(Up to 1 year)