Lenalidomide for Mild Cognitive Impairment

(MCLENA-1 Trial)

Recruiting at 1 trial location

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on the experience from a previous clinical trial with thalidomide, here, the investigators hypothesize that modulating both systemic and CNS inflammation via the pleiotropic immunomodulator lenalidomide is a putative therapeutic intervention for AD if administered at a proper time window during the course of the disease.

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.

What data supports the idea that Lenalidomide for Mild Cognitive Impairment is an effective drug?

The available research shows that Lenalidomide is being tested for its effects on mild cognitive impairment due to Alzheimer's disease. In a study called MCLENA-1, 30 patients with mild cognitive impairment are being treated with Lenalidomide to see if it can improve their thinking skills. The study also looks at safety and how the drug affects the brain. However, the research does not yet provide clear evidence of its effectiveness for this condition, as it is still in the testing phase. Most of the existing data on Lenalidomide is about its use in treating certain types of cancer, not cognitive impairment. ^{1 2 3 4 5}

What safety data exists for lenalidomide treatment?

Lenalidomide, also known as Revlimid, is primarily used for treating multiple myeloma and myelodysplastic syndromes. Common adverse effects include neutropenia, thrombocytopenia, thromboembolic events, gastrointestinal issues, skin eruptions, atrial fibrillation, and asthenia. There are also reports of lenalidomide-induced arthritis and decreased peripheral blood stem cell yield. In a Phase II trial for mild cognitive impairment due to Alzheimer's, safety and tolerability are being assessed through adverse events, vital signs, clinical biochemistry, and physical and neurological examinations. The trial aims to determine if lenalidomide is safe for Alzheimer's patients and can alter disease progression. ^{1 2 6 7 8}

Is the drug Lenalidomide a promising treatment for Mild Cognitive Impairment?

The provided research articles do not contain information about Lenalidomide or its effects on Mild Cognitive Impairment, so we cannot determine if it is a promising treatment based on this data. ^{9 10 11 12 13}

Research Team

Marwan N Sabbagh, M.D.

Principal Investigator

St. Joseph's Hospital and Medical Center, Phoenix

Boris Decourt, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. [2018]

2. New Zealand 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The potential of immunomodulatory drugs in the treatment of solid tumors. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. [2022]

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

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

8. Singapore pubmed.ncbi.nlm.nih.gov

Cutaneous adverse reactions to lenalidomide. [2018]

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

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

10. England pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Sex Is Associated with Adalimumab Side Effects and Drug Survival in Patients with Crohn's Disease. [2018]

13. England 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). [2022]