Lenalidomide for Smoldering Multiple Myeloma

Recruiting at 702 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Anticoagulants

Must not be taking: Bisphosphonates, Erythropoietin, Glucocorticosteroids

Disqualifiers: Seizure disorder, Hypertension, Heart failure, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 7

Duration: 24 weeks

226 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II/III trial studies how well lenalidomide works and compares it to observation in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use bisphosphonates during the trial, except for certain osteoporosis treatments. Also, you cannot use erythropoietin or glucocorticosteroids for myeloma treatment, but some other uses of glucocorticosteroids are allowed.

What data supports the effectiveness of the drug Lenalidomide for treating smoldering multiple myeloma?

Research shows that Lenalidomide, especially when combined with dexamethasone, can improve immune function in patients with high-risk smoldering multiple myeloma, potentially delaying the progression to full multiple myeloma. Additionally, Lenalidomide has been effective in treating multiple myeloma and other related conditions, suggesting its potential benefit for smoldering multiple myeloma. ^{1 2 3 4 5}

Is lenalidomide safe for use in humans?

Lenalidomide has been studied for safety in patients with lower-risk myelodysplastic syndromes, showing a higher rate of serious side effects compared to placebo, but these were manageable. Common mild side effects did not require stopping the treatment, and the risk of infections or new cancers was not increased. ^{6 7 8 9 10}

How is the drug Lenalidomide unique for treating smoldering multiple myeloma?

Lenalidomide is unique for treating smoldering multiple myeloma because it is an immunomodulatory drug that can delay the progression to active multiple myeloma, especially in high-risk patients, by enhancing the body's immune response and directly targeting cancer cells. Unlike other treatments, it is used early in the disease course to improve survival outcomes before symptoms develop. ^{1 2 3 11 12}

Research Team

Sagar Lonial

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with high-risk smoldering multiple myeloma who haven't had previous systemic or radiation therapy. They should have measurable M-protein levels and meet certain blood and biochemical standards. Women of childbearing age must follow strict pregnancy testing and contraception rules. HIV+ individuals can join if they meet additional criteria, but those with active infections, severe neuropathy, advanced heart failure, or immediate need for chemotherapy are excluded.

Inclusion Criteria

You must have a detectable amount of M-protein in your blood.

I am HIV positive and meet the specific health criteria.

I meet the medication and medical history requirements.

Exclusion Criteria

I do not urgently need chemotherapy.

I do not have a condition known as monoclonal gammopathy of undetermined significance.

I do not have severe numbness or pain in my hands or feet.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive lenalidomide orally once daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

24 weeks

Assessed every 4 weeks

Observation

Patients undergo observation until progression to symptomatic myeloma.

Varies until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

10 years

Every 3 months for 2 years, every 6 months for 3 years, then annually for 5 years

Treatment Details

Interventions

• Lenalidomide

Trial Overview The study is examining the effectiveness of lenalidomide compared to just watching and waiting in patients with asymptomatic high-risk smoldering multiple myeloma. It's a randomized trial where some people will receive the drug while others won't get any treatment unless their condition worsens.

Participant Groups

Group I: Arm A (lenalidomide) Experimental Treatment 2 Interventions

Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (observation) Active Control 2 Interventions

Patients undergo observation until progression to symptomatic myeloma.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Lenalidomide is a powerful treatment for multiple myeloma (MM) that works by directly causing cancer cell death, preventing cancer cells from sticking to bone marrow, and enhancing the body's immune response against tumors.

In combination with dexamethasone, lenalidomide has shown superior effectiveness in clinical trials, leading to improved patient outcomes such as longer survival and FDA approval for treating relapsed MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Hideshima, T., Raje, N., Richardson, PG., 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]

Lenalidomide significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation, as shown in randomized trials like the FIRST and MM-015 trials.

Continuous lenalidomide therapy is associated with less toxicity compared to thalidomide, maintaining tolerability without increasing the risk of neutropenia or second primary malignancies, making it a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. McCormack, PL.[2018]

Lenalidomide (Revlimid) has been rapidly developed and recently approved for treating relapsed multiple myeloma, showing durable clinical responses, especially when combined with dexamethasone.

Clinical trials indicate that lenalidomide is generally well tolerated by patients, with manageable side effects, making it a promising option for those with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. Richardson, PG., Mitsiades, C., Hideshima, T., et al.[2018]

Real-world evidence from psoriasis registries involving 6059 adult patients shows that adalimumab has a consistent long-term safety profile, with an overall adverse event rate of 22.2 per 100 patient-years.

The incidence of serious adverse events was relatively low at 4.3 per 100 patient-years, and specific concerns such as infections and malignancies were reported at rates that align with previous clinical studies, reinforcing the safety of adalimumab in treating psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the real-world evidence of adalimumab safety in psoriasis registries. Strober, B., Crowley, J., Langley, RG., et al.[2019]

In a phase 3 trial involving 239 patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), lenalidomide showed a higher incidence of grade 3-4 treatment-emergent adverse events (86% vs. 44% for placebo), but did not increase the risk of infections or bleeding events.

Despite the higher incidence of severe adverse events, lenalidomide demonstrated a predictable and manageable safety profile, allowing for continued therapy to maximize clinical benefits in patients who were ineligible or refractory to erythropoiesis-stimulating agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial. Almeida, A., Fenaux, P., Garcia-Manero, G., et al.[2019]

In a systematic review of 10 RCTs and 51 observational studies, infliximab was associated with a higher risk of treatment discontinuation and serious infections compared to abatacept, adalimumab, and etanercept in patients with rheumatoid arthritis (RA).

The safety profile of targeted immunomodulators generally favored abatacept, adalimumab, and etanercept over infliximab, although there was insufficient evidence to compare other TIMs or assess safety outcomes in non-RA populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. Desai, RJ., Thaler, KJ., Mahlknecht, P., et al.[2022]

In a phase IIb study involving 25 lenalidomide-refractory multiple myeloma patients, the combination of vorinostat, lenalidomide, and dexamethasone showed an overall response rate of 24% and a clinical benefit rate of 80%, indicating significant activity in this challenging patient population.

The most common severe side effects included neutropenia (48%) and thrombocytopenia (32%), highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens. Sanchez, L., Vesole, DH., Richter, JR., et al.[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]

References

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

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. [2018]

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

Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis. [2021]

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

Lenalidomide in multiple myeloma. [2018]

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

Brodalumab: 4-Year US Pharmacovigilance Report. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Systematic review of the real-world evidence of adalimumab safety in psoriasis registries. [2019]

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

Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial. [2019]

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

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review. [2022]

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

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens. [2018]

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

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

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

Management of asymptomatic myeloma patients. [2015]