Pilot Study of Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in hs-CTRP levels in peripheral blood during statin therapy
研究概览
简要总结
Patients with clonal cytopenia of undetermined significance (CCUS) and lower-risk myelodysplastic syndromes (MDS) have a life expectancy of 5 to 10 years. Mortality in these patients results from progression of disease to higher-risk MDS or acute myeloid leukemia (AML) and cardiovascular events. Currently there are no FDA-approved treatments with the potential to improve survival of patients with CCUS and lower-risk MDS. Statins are an appealing class of drugs to consider in this situation as preclinical data support their potential to suppress progression of myeloid malignancy, and they have a well-established role in prevention of major cardiovascular events. This is a pilot study to explore the role of statins in treatment of patients with CCUS and lower-risk MDS. In this study, change in inflammatory biomarkers and variant allele frequency (VAF) of somatic mutations will be used as a surrogate marker of response to statin therapy. The hypothesis is that the use of statins at diagnosis of CCUS or lower-risk MDS will reduce inflammation and delay or prevent the expected increase in the VAF of somatic mutations over time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Diagnosis of CCUS or lower-risk MDS as defined below:
- •CCUS is defined as the presence of somatic mutation(s) in recurrently mutated genes identified through the clinical MyeloSeq assay with a VAF ≥ 2% in the absence of bone marrow morphology/cytogenetic changes diagnostic of MDS PLUS unexplained persistent cytopenia in at least one lineage for at least 6 months:
- •Hemoglobin < 11.3 g/dL in females or < 13 g/dL in males
- •ANC < 1.8 x 109/L
- •Platelets < 150 x 109/L
- •MDS is defined using the WHO 2016 definition and classified into lower-risk if IPSS-R score is ≤ 3.5 . Lower-risk MDS will be required to have at least one mutation in a recurrent mutated gene with a VAF ≥ 2%.
- •Patient must be transfusion independent.
- •At least 18 years of age.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •CCUS patients with cytogenetic change alone.
- •Current or prior use of disease-modifying therapy (e.g., lenalidomide, Luspatercept, Imitelstat, HMAs, venetoclax) with any dose within the last 3 months, with the exception of concurrent use of erythropoetin stimulating agents
- •Prior use of a statin within 1 year prior to start of treatment.
- •A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence active of disease.
- •Currently receiving any investigational agent for CCUS/MDS. The minimum interval between the last dose of investigational agent used for CCUS/MDS and Day 1 of this trial should be 5 half-lives of the investigational agent.
- •A history of allergic reactions or intolerance attributed to compounds of similar chemical or biologic composition to atorvastatin, rosuvastatin, any other statin, or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic infection, sepsis, or active liver disease (acute liver failure, decompensated cirrhosis, or persistent elevation in ALT or AST > 3 x ULN), or any other comorbidity that would preclude statin use based on FDA recommendation.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- •Patients with HIV and HCV are not eligible for the trial if they are concomitantly receiving active treatment for HIV/HCV given the concern for potential drug interactions. The minimum interval between the last dose of antiviral and enrollment into the study should be 28 days or 5 half-lives of the antiviral drug, whichever is longer. The liver function profile of eligible HIV/HCV patients must be within the acceptable limits.
研究组 & 干预措施
Atorvastatin
- Choice of statin is at the discretion of the treating physician and may depend on insurance approval.
- Atorvastatin dosing starts at 80 mg once daily.
- In the absence of disease progression or intolerable side effects, patients may receive up to 12 months of treatment.
- If a patient switches statins due to toxicity, treatment time is still limited to 12 months total (ie, if a patient receives 6 months of atorvastatin and switches to rosuvastatin, the duration of rosuvastatin will be no more than 6 months).
干预措施: Atorvastatin (Drug)
Rosuvastatin
- Choice of statin is at the discretion of the treating physician and may depend on insurance approval.
- Rosuvastatin dosing starts at 40 mg once daily.
- In the absence of disease progression or intolerable side effects, patients may receive up to 12 months of treatment.
- If a patient switches statins due to toxicity, treatment time is still limited to 12 months total (ie, if a patient receives 6 months of atorvastatin and switches to rosuvastatin, the duration of rosuvastatin will be no more than 6 months).
干预措施: Rosuvastatin (Drug)
结局指标
主要结局
Change in hs-CTRP levels in peripheral blood during statin therapy
时间窗: Pre-treatment, every 3 months while on treatment, end of treatment, 3 months after end of treatment and time of progression (estimated to be 15 months)
次要结局
- Change in allele burden (VAF) of somatic mutation(Pre-treatment, every 3 months while on treatment, end of treatment, 3 months after end of treatment and time of progression (estimated to be 15 months))