Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)

Trial Title: Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)

NCT ID: NCT05483010

Condition: Clonal Cytopenia of Undetermined Significance
Myelodysplastic Syndromes

Conditions: Official terms:
Preleukemia
Myelodysplastic Syndromes
Cytopenia
Anemia
Leukopenia
Thrombocytopenia
Syndrome
Atorvastatin
Rosuvastatin Calcium

Conditions: Keywords:
CCUS
MDS
Statins
Inflammation

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Atorvastatin
Description: Atorvastatin is commercially available.
Arm group label: Atorvastatin

Other name: Lipitor

Intervention type: Drug
Intervention name: Rosuvastatin
Description: Rosuvastatin is commercially available.
Arm group label: Rosuvastatin

Other name: Crestor

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Washington University School of Medicine

Address:
City: Saint Louis
Zip: 63110
Country: United States

Status: Recruiting

Contact:
Last name: Amber Afzal, M.D., MSCI

Phone: 314-273-0564
Email: afzalamber@wustl.edu

Investigator:
Last name: Amber Afzal, M.D., MSCI
Email: Principal Investigator

Investigator:
Last name: Meagan Jacoby, M.D., Ph.D.
Email: Sub-Investigator

Investigator:
Last name: Matthew Walter, M.D.
Email: Sub-Investigator

Investigator:
Last name: Feng Gao, Ph.D.
Email: Sub-Investigator

Start date: February 19, 2024

Completion date: May 31, 2027

Lead sponsor:
Agency: Washington University School of Medicine
Agency class: Other

Source: Washington University School of Medicine

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05483010
http://www.siteman.wustl.edu