Lenalidomide for Mild Cognitive Impairment

(MCLENA-1 Trial)

No longer recruiting at 2 trial locations

Overseen By Marwan N Sabbagh, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Must be taking: Cholinesterase inhibitors, Memantine

Disqualifiers: Neurological illness, Major psychiatric disorder, Alcohol abuse, Hypertension, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if lenalidomide (Revlimid) can assist individuals with mild cognitive impairment (MCI) by reducing inflammation in the body and brain, which may contribute to Alzheimer's disease. Participants will take either lenalidomide or a placebo daily for one year, followed by a six-month break to observe changes in their condition. Ideal candidates are adults diagnosed with amnestic MCI, a type of memory loss, who can take oral medication and have someone to assist with study visits. As a Phase 2 trial, this research measures lenalidomide's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings in Alzheimer's treatment.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, you can stay on stable doses of a cholinesterase inhibitor and/or memantine if they have been stable for at least 90 days before the trial and are expected to remain stable during the study.

Is there any evidence suggesting that lenalidomide is likely to be safe for humans?

Research shows that lenalidomide is generally well-tolerated by patients. In earlier studies, individuals taking lenalidomide for mild memory problems mostly experienced mild to moderate side effects. Tiredness and nausea were the most common, but these were usually manageable. These studies reported no serious side effects directly caused by lenalidomide. Additionally, lenalidomide is already approved for other uses, indicating a well-understood safety profile. While this does not guarantee safety for everyone, it offers some reassurance about its overall safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for mild cognitive impairment, which often include medications like donepezil and others that primarily target neurotransmitter activity, lenalidomide offers a fresh approach. Lenalidomide is unique because it modulates the immune system and has anti-inflammatory properties, which researchers believe could play a crucial role in slowing down cognitive decline. By addressing inflammation, which is increasingly recognized as a factor in neurodegenerative conditions, lenalidomide could offer benefits that current treatments do not. Researchers are excited about this potential dual-action approach, which could lead to more comprehensive management of mild cognitive impairment.

What evidence suggests that lenalidomide might be an effective treatment for Alzheimer's disease?

Research has shown that lenalidomide, which participants in this trial may receive, might help with memory and thinking problems by reducing inflammation linked to Alzheimer's disease. Studies have found that lenalidomide can improve overall brain function in some patients. This improvement relates to changes in certain proteins in the brain fluid associated with inflammation. Simply put, lenalidomide appears to work by lowering inflammation, which is believed to contribute to brain changes in Alzheimer's. These findings suggest that lenalidomide could be a promising treatment for mild memory and thinking issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Boris Decourt, PhD

Principal Investigator

The Cleveland Clinic

Marwan N Sabbagh, M.D.

Principal Investigator

St. Joseph's Hospital and Medical Center, Phoenix

Are You a Good Fit for This Trial?

This trial is for men and women aged 50-89 with amnestic MCI, a type of memory loss. Participants need an MMSE score of 22-28, stable health conditions, and must not be at risk of pregnancy. They should have no severe diseases or recent psychiatric disorders that could affect dementia.

Inclusion Criteria

I can take pills by mouth.

Legally authorized representative (LAR) review and sign the informed consent form if applicable

I can attend all required study visits.

Exclusion Criteria

I have been diagnosed with multiple myeloma before.

I have not had a heart attack or unstable heart disease in the past year.

Use of any investigational medical device within two weeks before screening or after end of the present study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide 10 mg/day or placebo daily for 12 months

12 months

Washout

Participants undergo a 6-month washout period to assess the effects of treatment discontinuation

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide

Trial Overview The MCLENA-1 trial tests if Lenalidomide can help people with mild cognitive impairment by reducing inflammation in the brain. Patients will either receive Lenalidomide or a placebo to compare effects.

How Is the Trial Designed?

Group I: Lenalidomide Experimental Treatment 1 Intervention

Lenalidomide 10 mg/day taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration.

Group II: Placebo Placebo Group 1 Intervention

Placebo taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Lenalidomide is an effective treatment for patients with relapsed or refractory multiple myeloma, showing promising clinical activity and is approved by the FDA.

Common side effects of lenalidomide include neutropenia, thrombocytopenia, and thromboembolic events, necessitating careful monitoring to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. Tariman, JD.[2018]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

Adalimumab (ADA) is an effective treatment for rheumatoid arthritis (RA) and other inflammatory conditions, and can be used alone or with other medications like methotrexate.

This study compares the safety and effectiveness of ADA with other TNF-α inhibitors, etanercept and infliximab, highlighting the need for more direct comparisons in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. Voulgari, PV., Kaltsonoudis, E., Papagoras, C., et al.[2022]

Golimumab demonstrated long-term efficacy in treating psoriatic arthritis (PsA), maintaining significant clinical improvement over 5 years, with ACR20 response rates between 62.8% and 69.9% and DAS28-CRP response rates from 75.2% to 84.9%.

The treatment effectively inhibited radiographic progression in PsA, with minimal changes in PsA-modified Sharp scores, and no new safety concerns were identified, indicating it is a safe long-term option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study). Kavanaugh, A., McInnes, IB., Mease, P., et al.[2022]

Lenalidomide, while effective as a maintenance treatment for mantle-cell lymphoma, can induce rare adverse events such as arthritis, as demonstrated in a case study of a 71-year-old patient who developed scapular-belt arthritis after treatment.

Pharmacovigilance data revealed that arthritis is a rare side effect of lenalidomide, with only three reported cases in France and accounting for just 0.13% of adverse events in the international VigiBase® database, highlighting the need for awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. Icard, C., Mocquot, P., Nogaro, JC., et al.[2022]

In a study involving 15,132 patients with rheumatoid arthritis, adalimumab was found to have a well-established safety profile, with serious infections occurring at a low rate of 4.7 events per 100 patient-years and no significant laboratory abnormalities compared to placebo.

The analysis also indicated that pregnancy outcomes for women exposed to adalimumab were similar to those of unexposed women with rheumatoid arthritis and healthy women, with no increased risk of major birth defects or spontaneous abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Burmester, GR., Landewé, R., Genovese, MC., et al.[2022]

Lenalidomide, a derivative of thalidomide, has improved potency and a better side-effect profile, particularly with reduced neurologic toxicity compared to its predecessor.

While lenalidomide shows promise in treating conditions like myelodysplastic syndrome and multiple myeloma, there are still concerns about pro-thrombotic effects, especially when used with dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. Crane, E., List, A.[2018]

In a study of 188 patients with Crohn's disease treated with adalimumab (ADA), male patients had a significantly higher drug survival rate (48.1%) compared to female patients (30.8%), indicating that gender may influence treatment outcomes.

Female patients reported more side effects (81.3% vs. 64.2%) and were more likely to stop ADA treatment due to these side effects (35.4% vs. 18.4%), suggesting a need for tailored treatment strategies for women to improve their drug survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex Is Associated with Adalimumab Side Effects and Drug Survival in Patients with Crohn's Disease. Lie, MR., Kreijne, JE., van der Woude, CJ.[2018]

Lenalidomide (REVLIMID®) is an effective treatment for multiple myeloma and transfusion-dependent anemia in myelodysplastic syndromes, showing better activity and less neurotoxicity compared to its predecessor, thalidomide.

This drug has multiple beneficial properties, including anti-inflammatory and antiangiogenic effects, and may play a significant role in treating various cancers beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of immunomodulatory drugs in the treatment of solid tumors. Dalgleish, A., Galustian, C.[2018]

Golimumab, an anti-TNF monoclonal antibody, has been shown to be more effective than methotrexate alone in improving symptoms of rheumatoid arthritis in two large trials involving methotrexate-naïve and -experienced patients.

In addition to rheumatoid arthritis, golimumab demonstrated significant efficacy in treating psoriatic arthritis and ankylosing spondylitis, with a favorable safety profile similar to other anti-TNF therapies, indicating its broad therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golimumab: in the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Oldfield, V., Plosker, GL.[2018]

Lenalidomide is an effective immunomodulatory drug primarily used to treat multiple myeloma, myelodysplastic syndromes, and amyloidosis, but it can cause significant adverse reactions.

The review specifically highlights cutaneous adverse reactions associated with lenalidomide, which include skin eruptions, alongside other serious side effects like myelosuppression and venous thromboembolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous adverse reactions to lenalidomide. Imbesi, S., Allegra, A., Calapai, G., et al.[2018]

This Phase II study will evaluate the safety and cognitive effects of lenalidomide in 30 patients with amnestic mild cognitive impairment (aMCI) over 12 months, aiming to determine if it can alter the progression of Alzheimer's disease (AD).

The study will also assess lenalidomide's impact on brain amyloid levels and neurodegeneration using advanced imaging techniques, potentially establishing it as the first drug to delay AD progression if proven effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease. Decourt, B., Wilson, J., Ritter, A., et al.[2021]

Lenalidomide has become a crucial treatment option for multiple myeloma and del-5q myelodysplastic syndromes, and it has been tested for various other cancers, showcasing its broad therapeutic potential.

The drug received FDA approval for use in combination with dexamethasone for previously treated multiple myeloma, highlighting its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. Galustian, C., Dalgleish, A.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7051033/

MCLENA-1: A Phase II Clinical Trial for the Assessment of ... 30 amnestic mild cognitive impairment (aMCI) subjects will be treated with lenalidomide at 10 mg/day for 12 months on a 1:1 ratio, followed by a 6 months ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1879406825001377

Treatment-related cognitive changes in multiple myeloma The meta-analysis revealed a significant cognitive decline from baseline across all treatment during the first six months of treatment (standardized mean ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04032626

Study Details | NCT04032626 | MCLENA-1: A ... ... Efficacy of Lenalidomide in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease. Conditions. Cognitive Impairment, MildCognitive Dysfunction ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.072340

Mclena‐1: A Phase II Clinical Trial for the Assessment of ... This is a Phase II, proof-of mechanism, placebo-controlled clinical study on amnestic mild cognitive impairment (aMCI) male and female subjects ...

5. dovepress.com dovepress.com/outcome-of-lenalidomide-treatment-for-cognitive-impairment-caused-by-i-peer-reviewed-fulltext-article-JIR

Outcome of Lenalidomide Treatment for Cognitive ... The overall cognitive function of some patients improved significantly after lenalidomide treatment, and the changes of CSF cytokines during ...

6. ecommons.roseman.edu ecommons.roseman.edu/cgi/viewcontent.cgi?article=1254&context=researchsymposium

MCLENA-1: a Phase II clinical trial for the assessment of ... The primary objective of the study is to determine the effect of 12 months of lenalidomide treatment on cognition, which is assessed via a battery of cognitive ...

7. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/lenalidomide-for-early-alzheimers-taking-on-multiple-neuropathologies-at-once-1

Lenalidomide for Early Alzheimer's: Taking on Multiple ... One study is a phase 1b-2a investigation examining short-term use of lenalidomide (six months) with a focus on safety and effect on biomarkers.