A Phase I Study of Epigenetic Immunomodulation Through the Use of Azacitidine, Lenalidomide, and Grifola Frondosa in Patients With Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of Grifola frondosa extract, azacitidine, and lenalidomide that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
详细描述
Study Drugs:
Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better.
Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease the growth of cancer cells.
Grifola frondosa extract is a natural substance taken from maitake mushrooms. Researchers want to learn if it can cause the body's immune system to react against cancer.
Study Groups:
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
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed diagnosis of an advanced solid tumor refractory to standard treatment or for which no standard therapy is available.
- •Patients must have ECOG performance status 2 or better (0-2).
- •Patients must have normal organ and marrow function as defined: Absolute lymphocyte count > 1,000 /uL, Absolute neutrophil count > 1,500 /uL, Platelets > 75,000 /uL, Bilirubin </= 1.5 * ULN and AST and/or ALT </= 2.5 * the institutional upper limit of normal (ULN), </= 5 * ULN for patients with liver metastases, Serum creatinine within normal limits; if abnormal, then a calculated creatinine clearance >/= 50 mL/min
- •Patients must be able to understand and be willing to sign an IRB-approved written informed consent document.
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide.FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. 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 (ie, has had menses at any time in the preceding 24 consecutive months).
- •Patients must be 18 years of age or older since the safety and dosages of these study drugs has not been demonstrated in the pediatric population. Exception: patients who are 13 years old or older and have more than 50 kg of body weight will be eligible after consultation with their pediatric attending.
- •Life expectancy greater than 3 months based on the attending physician's discretion.
- •All study participants must be registered in the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, symptomatic cardiac arrhythmia, active bleeding, active thrombosis, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of stroke or transient ischemic attack within 6 months prior to study enrollment and significant vascular disease (e.g., aortic aneurysm, aortic dissection) and symptomatic peripheral vascular disease.
- •History of allergic reactions to the study drugs or their analogs.
- •Patients that have had any treatment specific for tumor control within 3 weeks of study drug treatment or: a. within 2 weeks if cytotoxic agents were given weekly b. within 6 weeks for nitrosoureas or mitomycin C c. within 4 half-lives for targeted agents with half lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents) d. failed to recover from toxic effects of any therapy prior to study entry
- •Concurrent known immunosuppressors.
- •Inability to swallow oral medication.
- •Pregnant or breastfeeding women.
- •Concurrent enrollment on another research study.
- •Known hepatitis B and C infection, HIV infection and autoimmune disorders.
- •Subjects with known moderate or severe renal impairment will be excluded if creatinine clearance < 60 ml/min.
研究组 & 干预措施
Azacitidine + Lenalidomide
Azacitidine 75 mg/m2 subcutaneous or by vein on days 1 - 5 of a 28 day cycle. Lenalidomide starting dose 10 mg by mouth daily on days 1-21 of a 28 day cycle, until maximum tolerated dose (MTD) reached. MTD used for combination and expansion groups.
干预措施: Azacitidine (Drug)
Azacitidine + Lenalidomide + Grifola Frondosa
Once Lenalidomide MTD identified in combination with azacitidine, Grifola frondosa added. Cycle 1, azacitidine on day 1, lenalidomide on day 2 and Grifola frondosa on day 3. Azacitidine daily for 5 days every 28 days while lenalidomide and Grifola frondosa on days 1-21 of subsequent cycles.
干预措施: Azacitidine (Drug)
Azacitidine + Lenalidomide + Grifola Frondosa
Once Lenalidomide MTD identified in combination with azacitidine, Grifola frondosa added. Cycle 1, azacitidine on day 1, lenalidomide on day 2 and Grifola frondosa on day 3. Azacitidine daily for 5 days every 28 days while lenalidomide and Grifola frondosa on days 1-21 of subsequent cycles.
干预措施: Lenalidomide (Drug)
Azacitidine + Lenalidomide + Grifola Frondosa
Once Lenalidomide MTD identified in combination with azacitidine, Grifola frondosa added. Cycle 1, azacitidine on day 1, lenalidomide on day 2 and Grifola frondosa on day 3. Azacitidine daily for 5 days every 28 days while lenalidomide and Grifola frondosa on days 1-21 of subsequent cycles.
干预措施: Grifola Frondosa (Drug)
Expansion Group A
Azacitidine + Lenalidomide MTD, then 2 weeks later Grifola frondosa
干预措施: Lenalidomide (Drug)
Expansion Group B
Azacitidine + Grifola Frondosa, then 2 weeks later Lenalidomide
干预措施: Lenalidomide (Drug)
Azacitidine + Lenalidomide
Azacitidine 75 mg/m2 subcutaneous or by vein on days 1 - 5 of a 28 day cycle. Lenalidomide starting dose 10 mg by mouth daily on days 1-21 of a 28 day cycle, until maximum tolerated dose (MTD) reached. MTD used for combination and expansion groups.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 4 weeks
MTD defined by patient dose limiting toxicities (DLTs) that occur in the first cycle (4 weeks).
次要结局
未报告次要终点