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

NCT05483010 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202211020
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Clonal Cytopenia of Undetermined Significance; Myelodysplastic Syndromes

Keywords

CCUS; MDS; Statins; Inflammation

Outcome Measures

Primary Outcomes (1)

• Change in hs-CTRP levels in peripheral blood during statin therapy

  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 (1)

• 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)

Study Arms (2)

Atorvastatin

EXPERIMENTAL

* 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).

Drug: Atorvastatin

Rosuvastatin

EXPERIMENTAL

* 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).

Drug: Rosuvastatin

Interventions

Atorvastatin DRUG

Atorvastatin is commercially available.

Also known as: Lipitor

Atorvastatin

Rosuvastatin DRUG

Rosuvastatin is commercially available.

Also known as: Crestor

Rosuvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Myelodysplastic Syndromes; Inflammation

Interventions

Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Study Officials

• Amber Afzal, M.D., MSCI

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amber Afzal, M.D., MSCI

CONTACT

314-273-0564; afzalamber@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 1, 2022
• Study Start: February 19, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication.
• Access Criteria: Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals.

Locations

US (1)