A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects With Relapsed or Refractory Acute Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.
详细描述
The Study Drug:
Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth and survival. By blocking the gene mutation, this may cause the cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 30 participants will be enrolled in the Phase I portion of the study, and up to 136 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ruxolitinib is found.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be >14 years of age
- •Must be diagnosed with refractory or relapsed AML or ALL.
- •Must have adequate organ function as demonstrated by the following: o Alanine Aminotransferase (ALT) (SGOT) and/or Aspartate Aminotransferase (AST) (SGPT) equal to or less than 1.5x upper limit of normal o Serum creatinine equal to or less than 2.5 mg/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
- •At least 2 weeks from prior leukemia-directed treatment to starting treatment drug (except for hydroxyurea, which is allowed if clinically indicated but should be stopped after 2 weeks of receiving study drug, and glucocorticoids, which are allowed but should be stopped upon starting treatment drug).
- •Treatment-related toxicities from prior therapies must have resolved to Grade equal to or less than 1 (except for peripheral neuropathy, which should resolve to grade equal to or less than 2)
- •No active malignancies with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- •Females of childbearing potential (FCBP)(A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) must have negative pregnancy test. FCBP and males participating in the study must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse while participating in the study and for at least 28 days after discontinuation from the study. If pregnancy or a positive pregnancy test does occur in a study subject, treatment with the study drug must be immediately discontinued.
排除标准
- •Known positive status for HIV, or known active hepatitis A, B, or C infection.
- •Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Pregnant or lactating females.
- •Acute promyelocytic leukemia
- •Concurrent use of strong inducers or strong inhibitors of cytochrome P450 3A4 (CYP3A4). Strong inducers are rifampin and St. John's Worth. Strong inhibitors are HIV-antivirals, clarythromycin, itraconazole, ketoconazole, nefazodone, and telithromycin.
- •Participating in any other research trial.
研究组 & 干预措施
Ruxolitinib 50 mg BID
Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.
干预措施: Ruxolitinib (Drug)
Ruxolitinib 100 mg BID
Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle.
干预措施: Ruxolitinib (Drug)
Ruxolitinib 200 mg BID
Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: End of first 28 day cycle for toxicity
MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort.
Maximum Tolerated Dose (MTD) of Ruxolitinib
时间窗: End of first 28 day cycle
The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy.
次要结局
- Participants With a Response(Up to 1 year)