Linvoseltamab + Lenalidomide for Multiple Myeloma

Overseen By Dickran Kazandjian, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Dickran Kazandjian, MD

Must be taking: Lenalidomide

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: Unknown

Duration: Up to 24 months

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether giving linvoseltamab with lenalidomide during maintenance treatment to participants with multiple myeloma will: 1. Get rid of any residual multiple myeloma cells in participants' bodies which is known as minimal residual disease negative (MRD-) status. For participants that start the study with residual multiple myeloma cells in participants' bodies: to determine how long you remain MRD-. 2. Increase the length of time that participants' disease is controlled. For participants with relapsed disease, to determine whether participants can re-attain MRD- status. 3. Increase the length of time that participants' disease responds to treatment. The researchers also want to find out the effects that linvoseltamab has on participants and participants' condition.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational agents or have contraindications to certain medications used in the study. It's best to discuss your specific medications with the study team.

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

Lenalidomide is a key drug in treating multiple myeloma, showing rapid and sustained control of the disease with manageable side effects. It works well when combined with other drugs like dexamethasone, improving survival rates in patients with relapsed or difficult-to-treat multiple myeloma. ^{1 2 3 4 5}

Is the combination of Linvoseltamab and Lenalidomide safe for humans?

Lenalidomide, used in treating multiple myeloma, has common side effects like fatigue, skin rash, and low blood cell counts, and can increase the risk of blood clots when combined with other drugs. Careful monitoring and managing these side effects are important to ensure safety. ^{1 6 7 8 9}

What makes the drug Linvoseltamab + Lenalidomide unique for treating multiple myeloma?

Linvoseltamab combined with Lenalidomide is unique because it potentially offers a novel approach by combining a new agent, Linvoseltamab, with Lenalidomide, an established immunomodulatory drug known for its effectiveness in multiple myeloma. This combination could enhance the treatment's effectiveness by leveraging the distinct mechanisms of both drugs. ^{1 5 10 11 12}

Research Team

Dickran Kazandjian, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for individuals with newly diagnosed multiple myeloma (NDMM) who are undergoing maintenance therapy. It aims to deepen response to treatment and achieve or maintain minimal residual disease negativity, especially after a relapse.

Inclusion Criteria

Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines

Willing and able to comply with clinic visits and study-related procedures

I have been diagnosed with multiple myeloma for the first time.

Exclusion Criteria

Patients who are receiving any other investigational agents unless deemed not to interfere with the study by the Principal Investigator (PI)

History of allergic reactions attributed to compounds of similar chemical or biologic composition to the experimental agents used in study

Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linvoseltamab in addition to lenalidomide during maintenance therapy for up to 24 cycles

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 4.5 years

Treatment Details

Interventions

• Lenalidomide
• Linvoseltamab

Trial Overview The study tests the combination of linvoseltamab and lenalidomide during maintenance therapy in NDMM patients. The goal is to eliminate remaining cancer cells, prolong disease control, and extend the duration of treatment response.

Participant Groups

Group I: Cohort 2 - Lenalidomide Treatment Group Experimental Treatment 2 Interventions

Participants in this group are currently receiving lenalidomide maintenance therapy but have relapsed disease within 12 months of starting maintenance will have Linvoseltamab added to lenalidomide maintenance and receive treatment with the combination for up to 24 cycles. Total participation duration is up to 4.5 years

Group II: Cohort 1 - Linvoseltamab Treatment Group Experimental Treatment 2 Interventions

Participants in this group are currently receiving lenalidomide maintenance therapy for ≤12 months will have linvoseltamab added to the lenalidomide maintenance therapy and receive treatment with the combination for up to 24 cycles. Total participation duration is up to 4.5 years

Who Is Running the Clinical Trial?

Dickran Kazandjian, MD

Lead Sponsor

Trials

1

Recruited

30+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Lenalidomide, when combined with dexamethasone, is a safe and effective treatment for newly diagnosed multiple myeloma patients who cannot undergo autologous stem cell transplantation, providing rapid disease control.

Long-term use of lenalidomide has led to significant improvements in progression-free survival for patients ineligible for stem cell transplantation and has resulted in deep, durable remissions for those with relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the use of lenalidomide for the treatment of multiple myeloma. Zagouri, F., Terpos, E., Kastritis, E., et al.[2018]

A subgroup analysis from two phase III clinical trials demonstrated that combining lenalidomide with dexamethasone is more effective than using dexamethasone alone for patients with relapsed or refractory multiple myeloma who had prior treatment with thalidomide.

This finding suggests that the lenalidomide and dexamethasone combination could be a more beneficial treatment option for these patients, potentially improving their outcomes in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. Meijer, E., Sonneveld, P.[2021]

Lenalidomide, when combined with dexamethasone (Len/Dex), significantly improves overall survival in patients with relapsed or refractory multiple myeloma compared to dexamethasone alone, as shown in pivotal phase III trials.

Lenalidomide has a manageable safety profile with minimal neurotoxicity, making it suitable for long-term use, and is also effective as an induction therapy for newly diagnosed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. Dimopoulos, MA., Terpos, E., Niesvizky, R.[2013]

Lenalidomide has shown significant efficacy in improving survival rates for patients with relapsed and refractory myeloma, especially when used alongside other treatments like bortezomib and thalidomide.

While lenalidomide is effective, it is associated with common side effects such as fatigue and thrombocytopenia, and its combination with other agents can increase the risk of blood clots, highlighting the importance of managing these adverse events for continued treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. van de Donk, NW., Görgün, G., Groen, RW., et al.[2021]

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]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

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]

In a phase 3 trial involving 559 patients with relapsed or refractory multiple myeloma who had previously received lenalidomide, the combination of pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared to bortezomib and dexamethasone alone, with a median survival of 11.20 months versus 7.10 months.

While the combination treatment showed better efficacy, it also resulted in higher rates of serious adverse events, particularly neutropenia and infections, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Richardson, PG., Oriol, A., Beksac, M., et al.[2020]

References

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

An update on the use of lenalidomide for the treatment of multiple myeloma. [2018]

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

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. [2021]

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

Immunomodulators in newly diagnosed multiple myeloma: current and future concepts. [2022]

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

Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. [2013]

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

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]

7. Singapore pubmed.ncbi.nlm.nih.gov

Cutaneous adverse reactions to lenalidomide. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

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

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

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

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. [2020]

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

Future directions in immunomodulatory therapy. [2015]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Thalidomide and lenalidomide in multiple myeloma. [2018]