What's the purpose of this trial?
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 variant allele frequency (VAF) of somatic mutations present at diagnosis 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 delay or prevent the expected increase in the VAF of somatic mutations over time.
This is an upcoming trial that has not yet started accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
* 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 cytopenia in at least one lineage:
* Hemoglobin \< 11.3 g/dL in females or \< 12.9 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%.
* 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).
* Eligible to receive HMAs, lenalidomide, or stem cell transplant at time of enrollment.
* Prior use of a statin within 6 months prior to enrollment.
* 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 enrollment into this trial should be 28 days or 5 half-lives of the investigational agent, whichever is longer.
* 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).
* 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.
Additional Trial Information
Enrollment: 16 patients (estimated)
Trial Sponsor: Washington University School of Medicine
SparkCures Identifier: 1489