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

Sponsor

Washington University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05483010

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Clonal Cytopenia of Undetermined Significance Myelodysplastic Syndromes	Drug: Atorvastatin Drug: Rosuvastatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Oct 31, 2025

Anticipated Study Completion Date :

Jan 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atorvastatin 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.	Drug: Atorvastatin Atorvastatin is commercially available. Other Names: Lipitor
Experimental: Rosuvastatin 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.	Drug: Rosuvastatin Rosuvastatin is commercially available. Other Names: Crestor

Arm

Intervention/Treatment

Experimental: Atorvastatin

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.

Drug: Atorvastatin

Atorvastatin is commercially available.

Other Names:

Lipitor

Experimental: Rosuvastatin

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.

Drug: Rosuvastatin

Rosuvastatin is commercially available.

Other Names:

Crestor

Outcome Measures

Primary Outcome Measures

Change in allele burden (VAF) of somatic mutation [From pre-treatment level to post-treatment level (estimated to be 12 months)]
-Assessed by next generation sequencing (NGS) performed on peripheral blood/bone marrow.

Secondary Outcome Measures

Event-free survival [Through completion of follow-up (estimated to be 15 months)]
-Defined as Time from diagnosis of CCUS/lower-risk MDS to development of higher-risk MDS/AML, major cardiovascular events, or all-cause mortality, whichever occurs first

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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).

Exclusion Criteria:

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.
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 are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.