Statins for Myelodysplastic Syndrome

Recruiting at 1 trial location

Overseen By Amber Afzal, M.D., MSCI

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Disease-modifying, Statins, Investigational agents, Antivirals

Disqualifiers: Other malignancy, Active liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 months

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether statins, commonly used to lower cholesterol, can benefit individuals with specific blood disorders called CCUS or lower-risk MDS. These conditions can lead to serious issues like leukemia or heart problems. Researchers hope statins might slow disease progression and reduce inflammation. Suitable candidates for this trial include those diagnosed with CCUS or lower-risk MDS, who are not currently on statin medication, and do not require regular blood transfusions. Participants will receive either atorvastatin (Lipitor) or rosuvastatin (Crestor or Rosuvastatin calcium) for up to a year, depending on their doctor's decision and insurance. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using certain disease-modifying therapies or investigational agents for CCUS/MDS. If you are on treatment for HIV or HCV, you must stop those medications at least 28 days before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that atorvastatin and rosuvastatin, the medications used in this trial, are generally safe for people. Atorvastatin has undergone extensive study and is known to sometimes cause changes in liver function and muscle pain, especially at high doses. However, these side effects are uncommon. In rare instances, reports of liver failure have occurred, but these are infrequent.

Rosuvastatin also has a strong safety record. In the JUPITER study, rosuvastatin proved so effective and safe that researchers stopped the study early due to positive results. Common side effects include muscle pain, but these are usually mild.

Both medications have FDA approval for lowering cholesterol, which adds confidence in their safety. While side effects can occur, they are generally rare and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using statins, like atorvastatin and rosuvastatin, for treating myelodysplastic syndrome (MDS) because these drugs might offer a new way to manage the condition. Unlike the typical treatments for MDS, which include blood transfusions, chemotherapy, and stem cell transplants, statins are traditionally used to lower cholesterol and have anti-inflammatory properties. This unique mechanism could potentially modify the disease process by reducing inflammation and possibly impacting the bone marrow environment in MDS patients. Additionally, statins are widely available and have a well-known safety profile, which could make them an accessible and cost-effective option if proven effective for MDS.

What evidence suggests that statins might be an effective treatment for myelodysplastic syndrome?

Research has shown that taking statins when diagnosed with myelodysplastic syndromes (MDS) links to lower death rates. One study found that starting statin treatment improved overall survival by 38% for MDS patients. In this trial, participants will receive either atorvastatin or rosuvastatin to evaluate their ability to reduce inflammation and slow harmful genetic changes. Rosuvastatin, in particular, improves cholesterol levels, which might help prevent heart problems. These findings suggest that statins could be a promising treatment for people with CCUS and lower-risk MDS by potentially extending life expectancy and slowing disease progression. ^{1 3 6 7 8}

Who Is on the Research Team?

Amber Afzal, M.D., MSCI

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with CCUS or lower-risk MDS, which are conditions related to blood cell production. Participants must have specific genetic mutations and low levels of hemoglobin, white cells, or platelets. They should not be pregnant, breastfeeding, or have untreated HIV/HCV. Those who've taken statins in the last 6 months or other cancer treatments within a month can't join.

Inclusion Criteria

Patient must be transfusion independent

My condition is either CCUS or lower-risk MDS.

I can understand and am willing to sign the consent form.

Exclusion Criteria

I do not have any serious illnesses that would stop me from safely taking statins.

I am allergic to atorvastatin, rosuvastatin, or similar medications.

I haven't used any disease-modifying therapy in the last 3 months, except for drugs that help produce red blood cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive statin therapy, either atorvastatin or rosuvastatin, for up to 12 months

12 months

Every 3 months while on treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit (in-person) at end of treatment, 1 visit (in-person) 3 months after end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Rosuvastatin

Trial Overview The study tests whether Atorvastatin and Rosuvastatin can reduce inflammation and slow down genetic changes in patients with CCUS/MDS. It aims to see if these common cholesterol-lowering drugs could extend life by preventing disease progression and cardiovascular events.

How Is the Trial Designed?

Group I: Rosuvastatin Experimental Treatment 1 Intervention

* 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).

Group II: Atorvastatin Experimental Treatment 1 Intervention

* 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).

Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Statins, specifically atorvastatin and fluvastatin, have been shown to induce differentiation and apoptosis in acute myeloid leukemia (AML) cells, suggesting their potential as therapeutic agents against this type of cancer.

Fluvastatin not only inhibited the growth of primary leukemic progenitors from AML patients but also enhanced the effectiveness of all-trans-retinoic acid (ATRA), indicating that combining statins with ATRA could help overcome resistance to ATRA in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive effects of statins on acute promyelocytic leukemia cells. Sassano, A., Katsoulidis, E., Antico, G., et al.[2018]

Rosuvastatin is a highly effective statin that can significantly lower LDL cholesterol levels by 52-63% and increase HDL cholesterol levels by up to 14%, making it superior to other statins like atorvastatin and simvastatin in improving cholesterol profiles.

It has a favorable safety profile, with minimal drug interactions due to its low metabolism by the CYP 450 enzyme system, and is well tolerated by patients, making it a reliable option for managing hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. Rosenson, RS.[2022]

Rosuvastatin (Crestor) is more effective than other statins in lowering low-density lipoprotein cholesterol (LDL-C), showing greater reductions across doses of 5-40 mg/day, and also increases high-density lipoprotein cholesterol while significantly reducing triglycerides.

In clinical trials, rosuvastatin was well tolerated with a low incidence of adverse events, demonstrating a safety profile similar to other statins, although long-term safety and effectiveness in preventing coronary events have not been established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. Lopez, LM.[2019]

Rosuvastatin is more effective than other statins like atorvastatin and simvastatin in lowering LDL cholesterol levels due to its higher affinity for the enzyme it inhibits, making it a strong option for patients needing significant LDL reduction.

While rosuvastatin can help patients reach LDL goals more quickly and with fewer side effects, it should be used cautiously due to a lack of long-term cardiovascular outcome data compared to other statins, and is recommended primarily for those who cannot tolerate other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin for the treatment of hypercholesterolemia. Culhane, NS., Lettieri, SL., Skae, JR.[2019]

In a case study of a patient with depressive disorder and high cardiovascular risk, switching to a combination of rosuvastatin and ezetimibe effectively managed cholesterol levels without interfering with the antitumor drug ruxolitinib.

The potential antidepressant effects of statins, along with cognitive-behavioral therapy, may have contributed to the patient's psychological improvement, highlighting the multifaceted benefits of statin therapy in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Importance of the individualized care process in a patient with recurrent acute coronary syndrome, multiple comorbidities and depressive syndrome]. Spinelli, A., Macchiusi, A., Di Fusco, SA., et al.[2022]

Rosuvastatin is an effective statin that significantly improves lipid profiles in patients with dyslipidemias, outperforming other statins like atorvastatin, pravastatin, and simvastatin in achieving LDL-C goals after 12 weeks of treatment.

The treatment is generally well tolerated, with low incidences of serious side effects, such as myopathy and elevated CPK levels, making rosuvastatin a safe first-line option for managing cholesterol in both low- and high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. Scott, LJ., Curran, MP., Figgitt, DP.[2018]

Rosuvastatin (Crestor) has been shown to significantly improve lipid profiles compared to other statins, leading to greater reductions in total and LDL cholesterol levels, and increases in HDL cholesterol, particularly at a standard dosage of 10 mg.

In phase III clinical trials, nearly 80% of patients at risk achieved LDL cholesterol levels below recommended targets with rosuvastatin, and its safety profile is comparable to other statins, with ongoing studies evaluating its long-term efficacy in preventing atherosclerosis and reducing cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Rosuvastatin (Crestor)]. Scheen, AJ.[2015]

A study involving over 10,000 veterans found that high-intensity atorvastatin therapy is associated with a higher incidence of adverse drug reactions (ADRs) compared to rosuvastatin, with ADR rates of 4.59% for atorvastatin versus 2.91% for rosuvastatin.

Specific ADRs such as abnormal liver transaminases and muscle symptoms were significantly more common in patients taking atorvastatin, indicating that while both medications are effective, atorvastatin may pose a greater risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of High-Intensity Statins in the Veteran Population: Atorvastatin 40 to 80 mg Compared With Rosuvastatin 20 to 40 mg. Stein, B., Ward, T., Hale, G., et al.[2020]

Rosuvastatin, currently in phase III clinical trials, shows promise in significantly lowering total cholesterol and LDL cholesterol levels in patients with high cholesterol, potentially more effectively than other statins.

However, there is not enough evidence to assess the safety of rosuvastatin or its impact on heart-related health outcomes, indicating that further research is needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? Ho, C.[2010]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10393730/

Statin use in myelodysplastic syndromes is associated with ... A retrospective study in a national cohort of patients with MDS to explore the effect of statins on overall survival (OS) and progression to leukemia.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e19063

Statins reduce mortality of patients with myelodysplastic ... Conclusions: Use of statins at time of MDS diagnosis is associated with reduced mortality among these patients. The beneficial effect of statins ...

3. bloodcancerstoday.com bloodcancerstoday.com/post/statin-use-linked-with-increased-mds-survival

Statin Use Linked with Increased MDS Survival Overall, the study showed starting statin therapy at MDS diagnosis was associated with a 38% improvement in OS, which was “higher than that ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05483010

NCT05483010 | Statins in Patients With Clonal Cytopenia ... Patients with clonal cytopenia of undetermined significance (CCUS) and lower-risk myelodysplastic syndromes (MDS) have a life expectancy of 5 to 10 years.

5. withpower.com withpower.com/trial/phase-2-preleukemia-9-2022-60c5a

Statins for Myelodysplastic Syndrome Trial Overview The study tests whether Atorvastatin and Rosuvastatin can reduce inflammation and slow down genetic changes in patients with CCUS/MDS. It aims to ...

6. pfe-pfizercom-prod.s3.amazonaws.com pfe-pfizercom-prod.s3.amazonaws.com/products/material_safety_data/LIPITOR_%28atorvastatin_calcium%29_tablets_25-may-2018.pdf

SAFETY DATA SHEET Clinical use of this drug has caused changes in liver function, muscle pain, weakness. at the highest dose used in the test.

7. fishersci.com fishersci.com/store/msds?partNumber=AC464810050&productDescription=ATORVASTATIN+CALCIUM+TRI+5GR&vendorId=VN00032119&countryCode=US&language=en

SAFETY DATA SHEET Skin and body protection. Wear appropriate protective gloves and clothing to prevent skin exposure. Page 3 / 7. Page 4. Atorvastatin calcium ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/020702s081lbl.pdf

LIPITOR® (atorvastatin calcium) tablets, for oral use There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including LIPITOR. Patients who consume ...