Ixazomib for Treatment of Chronic Graft vs. Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- Probability of Treatment Failure at 6 Months
研究概览
简要总结
This phase II trial studies how well ixazomib citrate works in treating patients with chronic graft-versus-host disease. Chronic graft-versus-host disease is a complication of a donor bone marrow or blood cell transplant, usually occurring more than three months after transplant, in which donor cells damage the host tissue. Ixazomib citrate may be an effective treatment for chronic graft-versus-host disease.
详细描述
PRIMARY OBJECTIVES:
I. Determine the proportion of subjects with treatment failure by 6 months of ixazomib (ixazomib citrate) treatment for chronic graft-versus-host disease (GVHD).
SECONDARY OBJECTIVES:
I. Determine 3 month overall (complete + partial), and complete response rate.
II. Determine 6 month overall (complete + partial), and complete response rate.
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
- •Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
- •Female patients who:
- •Are postmenopausal for at least 1 year before the screening visit, OR
- •Are surgically sterile, OR
- •If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
- •Agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- •Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
- •Agree to practice two effective contraception measures during the entire study treatment period and through 90 days after the last dose of study drug, OR
- •Agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- •Patients must have a diagnosis of a chronic GVHD according to the National Institute of Health (NIH) Consensus Criteria
- •Patients must have failed at least one prior line of systemic immune suppressive therapy for management of chronic GVHD
- •Absolute neutrophil count (ANC) >= 1,000/mm^3
- •Platelet count >= 75,000/mm^3; platelet transfusions are not allowed within 3 days before study enrollment
- •Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
- •Calculated creatinine clearance >= 30 mL/min
排除标准
- •Female patients who are lactating or have a positive serum pregnancy test during the screening period
- •Major surgery within 14 days before enrollment
- •Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care
- •Uncontrolled infection within 14 days before study enrollment
- •Infection treated with appropriate antimicrobial therapy and without signs of progression/treatment failure does not constitute an exclusion criterion
- •Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
- •Chronic hypertension on medical therapy does not constitute an exclusion criterion
- •Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
- •Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
- •Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- •Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- •Non-hematologic malignancy within the past 2 years with the exception of:
- •Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer
- •Carcinoma in situ of the cervix or breast
- •Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels
- •Cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study
- •Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
- •Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of start of this trial
- •New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment
- •Addition of a new systemic immune suppressive treatment simultaneously with ixazomib is also prohibited
- •Evidence of recurrent or progressive underlying malignant disease
- •Karnofsky performance status < 70%
- •Life expectancy less than 6 months
研究组 & 干预措施
Treatment (ixazomib citrate)
Patients receive ixazomib citrate PO once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.
干预措施: Ixazomib Citrate (Drug)
Treatment (ixazomib citrate)
Patients receive ixazomib citrate PO once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ixazomib citrate)
Patients receive ixazomib citrate PO once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.
干预措施: Quality-of-Life Assessment (Other)
Treatment (ixazomib citrate)
Patients receive ixazomib citrate PO once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Probability of Treatment Failure at 6 Months
时间窗: 6 months
Kaplan-Meier estimate assessed at 6 months for probability of treatment failure, defined as addition of a line of systemic immune-suppressive therapy, recurrent malignancy, or death.
Incidence of Adverse Events
时间窗: Up to 30 days following completion of study treatment
According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0
次要结局
- Biologic Studies(Up to 6 months)
- Probability of Non-relapse Mortality at 1 Year(1 year)
- Complete Response (CR) Rate(6 months)
- Cumulative Incidence of Primary Malignancy Relapse(1 year)
- Incidence of Discontinuation of All Systemic Immune Suppressive Therapies(1 year)
- Overall Response Rate (ORR) (Complete Response + Partial Response)(6 months)
- Probability of Failure-free Survival at 1 Year(1 year)
- Treatment Success(1 year)
- Use of Additional Systemic Immune Suppressive Therapies(1 year)
- Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)(1 year)
- Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)(1 year)
- Probability of Overall Survival at 1 Year(1 year)
- Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)(1 year)
- Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale(1 year)