Clinical trial NCT05483010: Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)
Official title: Pilot Study of Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Clonal Cytopenia of Undetermined Significance
Myelodysplastic Syndromes
Keywords: CCUS
MDS
Statins
Inflammation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2022-08-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in hs-CTRP levels in peripheral blood during statin therapy
timeFrame: 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)
Secondary outcomes:
measure: Change in allele burden (VAF) of somatic mutation
timeFrame: 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)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Amber Afzal, M.D., MSCI
role: PRINCIPAL_INVESTIGATOR
References: