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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05483010
• Other study ID #: 202211020
• Status: Recruiting
• Phase: Phase 2
• Start date: February 19, 2024
• Est. completion date: May 31, 2027

Study information

• Verified date: February 2024
• Source: Washington University School of Medicine
• Contact: Amber Afzal, M.D., MSCI
• Phone: 314-273-0564
• Email: afzalamber[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Clonal Cytopenia of Undetermined Significance
• Leukopenia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome
• Thrombocytopenia

Intervention

Drug:
• Atorvastatin
Atorvastatin is commercially available.
• Rosuvastatin
Rosuvastatin is commercially available.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in allele burden (VAF) of somatic mutation	-Assessed by next generation sequencing (NGS) performed on peripheral blood/bone marrow.	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)

External Links

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