Statins for Myelodysplastic Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Amber Afzal, M.D., MSCI

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if statins, drugs usually used to lower cholesterol, can help patients with certain blood disorders by reducing inflammation and slowing disease progression. These patients currently have no effective treatments and are at risk of their condition worsening. Statins are commonly prescribed medications that have multiple beneficial effects.

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 it safe to use statins like Rosuvastatin and Atorvastatin in humans?

Statins like Rosuvastatin (Crestor) and Atorvastatin (Lipitor) are generally considered safe for humans, with Rosuvastatin showing a lower incidence of side effects compared to Atorvastatin. Common side effects include liver enzyme changes and muscle symptoms, but these are relatively rare.

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How do statins like atorvastatin and rosuvastatin differ from other drugs for myelodysplastic syndrome?

Statins, such as atorvastatin and rosuvastatin, are unique because they not only lower cholesterol but also inhibit the growth of cancer cells and promote their death, which could be beneficial in treating conditions like myelodysplastic syndrome. This dual action is different from traditional treatments that may not target both cholesterol and cancer cell growth.

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Eligibility Criteria

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

I am 18 years old or older.

Patient must be transfusion independent

My condition is either CCUS or lower-risk MDS.

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University School of Medicine Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine Lead Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. [2018] Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment, rosuvastatin was significantly (all p

2. Belgium pubmed.ncbi.nlm.nih.gov

[Drug of the month. Rosuvastatin (Crestor)]. [2015] Rosuvastatin (Crestor) has been recently launched in Belgium by AstraZeneca. This new statin is indicated for the treatment of primary hypercholesterolaemia or combined dyslipidaemia, when changes in dietary habits are insufficient. Direct comparative randomised clinical trials with other statins demonstrated that rosuvastatin exerts a more favourable impact on lipid profile. When compared on a mg basis to other statins, rosuvastatin is associated with a greater reduction in total and LDL cholesterol levels and a greater increase of HDL cholesterol concentration, with a similar decrease in triglyceride levels. At the usual dosage of 10 mg, rosuvastatin allowed to reduce LDL cholesterol below recommended target levels for at risk patients among almost 80% of treated individuals in phase III clinical trials. If necessary, the daily dosage may be increased to 20 mg, or up to 40 mg (maximal dose), mostly in case of severe familial hypercholesterolaemia. Safety profile is good and similar to that of other commercialised statins. Rosuvastatin is currently evaluated in an extensive programme of randomised clinical trials (Galaxy programme) in order to demonstrate its efficacy in both prevention of atherosclerosis and reduction of cardiovascular morbidity and mortality.

3. United States pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. [2019] To summarize the relevant pharmacologic, clinical, and safety data regarding rosuvastatin (Crestor--AstraZeneca), the most recently marketed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of dyslipidemia.

4. Canada pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? [2010] (1) Rosuvastatin (Crestor(TM)) is a new synthetic agent for the treatment and prevention of lipid disorders, a risk factor for coronary heart disease. (2) Rosuvastatin is undergoing phase III clinical trials. A New Drug Application was submitted to the U.S. Food and Drug Administration in June, 2001. No information on the regulatory status in Canada is currently available. (3) Limited evidence from small clinical trials suggests that rosuvastatin may produce larger dose-dependent decreases in total cholesterol levels and low-density lipoprotein-cholesterol levels in hypercholesterolemic patients compared to other statins. There is insufficient evidence to draw conclusions about the safety of rosuvastatin. (4) The impact of rosuvastatin therapy on cardiac morbidity and mortality is not known. More experience is required to determine the effectiveness and relative benefits of this new drug.

5. United States 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. [2020] Background: High-intensity statin therapy is recommended in patients with clinical atherosclerotic cardiovascular disease (ASCVD) or at high risk of ASCVD. Current evidence demonstrates efficacy of high-intensity statin therapy in reducing major adverse cardiovascular events; yet the comparative safety profile between high-intensity statin agents remains unknown. In 2011, when atorvastatin became generic, the Veteran's Health Administration made the formulary switch from rosuvastatin to atorvastatin. Currently, rosuvastatin is generic; however, at the time of this study, it was still under patent. Objective: The primary objective was to determine if high-intensity atorvastatin compared with rosuvastatin is associated with an increased incidence of adverse drug reactions (ADRs) in the veteran population. Methods: A retrospective cohort study at James A. Haley Veterans' Hospital compared patients receiving rosuvastatin 20 to 40mg from January 2009 to November 2011 (n = 4,165) and atorvastatin 40 to 80mg from May 2012 to June 2016 (n = 5,852). Patients were excluded if they were nonadherent to statin therapy or had a documented ADR to atorvastatin prior to formulary switch. Results: A difference in overall ADR rates was found between atorvastatin and rosuvastatin groups (4.59% vs 2.91%; odds ratio [OR], 1.61; 95% CI, 1.29 to 2.00; P < 0.05). Statistically significant differences in abnormal liver transaminases (3.99% vs 1.39%; OR, 2.95; 95% CI, 2.21 to 3.94; P < 0.05) and statin-associated muscle symptoms (1.14% vs 0.5%; OR, 2.29; 95% CI, 1.39 to 3.74; P < 0.05) were identified between groups. Patients receiving rosuvastatin were on therapy 2.5 times longer before developing an ADR. Conclusion and Relevance: High-intensity atorvastatin compared with rosuvastatin is associated with an increased incidence of ADRs.

6. United States pubmed.ncbi.nlm.nih.gov

Rosuvastatin for the treatment of hypercholesterolemia. [2019] Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Because of its increased affinity for the reductase, rosuvastatin reduces the low-density lipoprotein cholesterol (LDL) level more than atorvastatin, simvastatin, and pravastatin do, without additional adverse effects. In addition, cytochrome P450 isoenzymes do not extensively metabolize rosuvastatin, and inhibitors of these isoenzymes do not substantially affect it. Rosuvastatin could be a first-line option for patients requiring a reduction of 50% or more to reach the LDL goal of the National Cholesterol Education Program Adult Treatment Panel III. Rosuvastatin monotherapy may allow patients to achieve this LDL goal earlier, and it may help them avoid combination therapy or potential adverse effects of high-dose statin therapy. However, because cardiovascular disease morbidity and mortality data are lacking for rosuvastatin (but available for all other marketed statins) and because its postmarketing data are limited, rosuvastatin should be reserved for patients requiring an LDL reduction of 50% or less who cannot reach the recommended goal with other statins because of adverse effects, drug interactions, or cost.

7. United States pubmed.ncbi.nlm.nih.gov

Suppressive effects of statins on acute promyelocytic leukemia cells. [2018] The family of statins includes pharmacologic inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase that are potent regulators of cholesterol biosynthesis. In addition to their cholesterol-lowering effects, statins inhibit cell proliferation and promote apoptosis of malignant cells in vitro, but their potential therapeutic roles in the treatment of malignancies remain to be defined. We examined the effects of statins on the growth and differentiation of acute myeloid leukemia (AML) cells. Atorvastatin and fluvastatin were found to be potent inducers of cell differentiation and apoptosis of the NB4 acute promyelocytic leukemia (APL) cell line. Such effects correlated with activation of the small G-proteins Rac1/Cdc42 and downstream engagement of the c-Jun NH(2)-terminal kinase kinase pathway, whose function was found to be essential for the generation of proapoptotic responses. Importantly, different statins were found to enhance all-trans-retinoic acid (ATRA)-dependent differentiation of APL blasts and reverse resistance to the antileukemic effects of ATRA. In addition, fluvastatin exhibited growth-inhibitory properties on primary bone marrow-derived leukemic progenitors from patients with AML and enhanced the suppressive effects of ATRA on leukemic progenitor colony formation. Altogether, these studies establish that statins exhibit potent antileukemic properties in vitro and raise the possibility that combinations of statins with ATRA may be an effective approach to overcome the development of ATRA resistance by the leukemic cells.

8. Italy pubmed.ncbi.nlm.nih.gov

[Importance of the individualized care process in a patient with recurrent acute coronary syndrome, multiple comorbidities and depressive syndrome]. [2022] Statins have pleiotropic effects, including anti-inflammatory action, which is class-specific and contributes to a reduction in cardiovascular events. Statins also have a potential antidepressant effect. We report the case of a patient with depressive disorder and very high cardiovascular risk, in whom idiopathic myelofibrosis was also diagnosed. Due to the potential interaction of the antitumor drug (ruxolitinib) with atorvastatin and sertraline at the level of cytochrome P450, the latter two drugs were discontinued. The patient was referred for cognitive-behavioral treatment and the combination of rosuvastatin/ezetimibe was prescribed. This drug combination led to the achievement of optimal cholesterol targets in the absence of metabolic interference with ruxolitinib and adverse events. This strategy allowed the continuation of antitumor therapy and led to a hematological improvement. The antidepressant effect of statins, in addition to cognitive-behavioral treatment, may have contributed to the improvement in the patient's psychological status.

9. England pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. [2022] Rosuvastatin (Crestor, AstraZeneca) is a synthetic statin that represents an advance on the pharmacologic and clinical properties of other agents in this class. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. Rosuvastatin is relatively hydrophilic and is selectively taken up by, and active in, hepatic cells. Rosuvastatin has the longest terminal half-life of the statins and is only minimally metabolized by the cytochrome P450 (CYP 450) enzyme system with no significant involvement of the 3A4 enzyme. Consistent with this finding is the absence of clinically significant drug interactions between rosuvastatin and other drugs known to inhibit CYP 450 enzymes. In patients with hypercholesterolemia, rosuvastatin 10-40 mg has been shown to reduce low-density lipoprotein cholesterol (LDL-C) levels by 52-63%, as well as increase high-density lipoprotein cholesterol (HDL-C) levels by up to 14% and reduce triglycerides (TG) by up to 28%. Studies have shown that rosuvastatin is superior to atorvastatin, simvastatin and pravastatin in reducing LDL-C and favorably modifying other components of the atherogenic lipid profile. The significant decreases in LDL-C with rosuvastatin treatment should help to improve attainment of lipid goals and reduce the requirement for dose titration. In addition, the effects of rosuvastatin on HDL-C and TG levels will be of benefit in treating patients with abnormalities such as mixed dyslipidemia and the metabolic syndrome. Rosuvastatin is well tolerated, with a safety profile comparable with that of other currently available statins.