Acalabrutinib for Chronic Graft-Versus-Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 51
- 试验地点
- 6
- 主要终点
- Best response (complete and partial response [CR + PR])
研究概览
简要总结
This phase II trial studies how well acalabrutinib works in treating patients with chronic graft versus host disease. Acalabrutinib may be an effective treatment for graft-versus-host disease caused by a stem cell transplant.
详细描述
OUTLINE:
Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 6 cycles with an option to continue for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Men and women ≥ 18 years of age
- •Moderate-severe chronic GVHD, diagnosed per the 2014 National Institutes of Health (NIH) criteria
- •Progression or recurrence of active chronic GVHD signs/symptoms after treatment with steroids
- •Karnofsky performance status >= 70%
- •Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib
- •Men must refrain from sperm donation during the study
- •Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
排除标准
- •Hospitalization for evaluation or management of an infection within the last 8 weeks
- •Change in immunosuppressive regimen within the 2 weeks prior to enrollment
- •Noncompliance
- •Treatment of chronic GVHD with ibrutinib
- •Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
- •Recurrent or prior malignancy (or any other malignancy that requires active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
- •Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- •Received a live virus vaccination within 28 days of first dose of study drug
- •Known history of infection with human immunodeficiency virus (HIV)
- •Uncontrolled, active significant infection (e.g., bacterial, viral, fungal or progressive multifocal leukoencephalopathy)
- •Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)
- •Active bleeding, history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
- •Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
- •Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
- •Requires warfarin or equivalent vitamin K antagonist
- •History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
- •Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
- •Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
- •Child-Pugh score of C for hepatic impairment
- •Total bilirubin > 2 mg/dL or alanine aminotransferase (ALT) > 2 x upper limit of normal, unless abnormalities are due to liver GVHD, in which case total bilirubin > 3 mg/dL or ALT 5 x upper limit of normal are exclusions
- •Absolute neutrophil count < 1.0 x 10^9/L or use of myeloid growth factors within the past 2 weeks
- •Platelet count < 50 x 10^9/L or platelet transfusion or thrombomimetic agent within the past 2 weeks
- •Glomerular filtration rate < 50 mL/min/1.73 m^2
- •Breastfeeding or pregnant
- •Concurrent participation in another clinical trial and receiving a non-Food and Drug Administration (FDA) approved medication
研究组 & 干预措施
Treatment (acalabrutinib)
Patients receive acalabrutinib 100 mg PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles with an option to continue for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Acalabrutinib (Drug)
Treatment (acalabrutinib)
Patients receive acalabrutinib 100 mg PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles with an option to continue for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Best response (complete and partial response [CR + PR])
时间窗: Within the first 6 months of treatment when the best response rate is known for each patient
The composite outcome of CR and PR, calculated according to the proposed response definitions of the 2014 National Institutes of Health Consensus Conference. Exact 95% confidence intervals (CI) will be calculated for the objective response rate using the Clopper and Pearson method. Will also compare the observed best ORR with the published efficacy of ibrutinib (67%) and provide the 95% CI for the difference.
次要结局
- Duration of response (DOR)(From the date the PR is documented until loss of the response or start of another systemic immunosuppressive treatment for chronic graft versus host disease (GVHD), whichever occurs first, assessed up to 3 years)
- Change in patient-reported outcomes: Lee Chronic GVHD Symptom Scale score(Baseline up to 3 years)
- Failure-free survival(At 6 months and 1 year)
- Organ-specific response rates(Up to 3 years)
- Incidence of adverse events (AEs)(Up to 30 days following the last dose of acalabrutinib)
- Change in patient-reported outcomes: Patient-Reported Outcomes Measurement Information System-29(Baseline up to 3 years)