Lenalidomide + Dexamethasone +/- Bortezomib for Multiple Myeloma

Not currently recruiting at 571 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants

Disqualifiers: Infections, Heart failure, Hypertension, Diabetes, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding bortezomib (Velcade) to the standard treatment of lenalidomide (Revlimid) and dexamethasone (Decadron, Dexone, Hexadrol) is more effective for people with multiple myeloma, a type of blood cancer. The trial includes two groups: one receives lenalidomide and dexamethasone, while the other receives those drugs plus bortezomib. The goal is to determine which combination best stops the growth and spread of cancer cells. This trial targets individuals newly diagnosed with multiple myeloma who have not undergone chemotherapy and can identify their condition through measurable disease. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have received prior chemotherapy, bortezomib, or lenalidomide for multiple myeloma, and you must be able to take aspirin or enoxaparin unless you are already on anticoagulation therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of lenalidomide, bortezomib, and dexamethasone is generally well-tolerated by people with newly diagnosed multiple myeloma. Studies have found this combination to be effective and reasonably safe for patients. Notably, nearly two-thirds of patients with relapsed or difficult-to-treat myeloma have experienced significant improvements with this treatment.

Each drug in this combination plays a specific role: lenalidomide aids the immune system and may block blood vessels that feed tumors, bortezomib inhibits cancer cell growth, and dexamethasone kills cancer cells in various ways. While these treatments can cause side effects, they are usually manageable.

These findings suggest that the treatment is promising and often well-tolerated. However, as with any treatment, individuals may experience different effects, so discussing potential risks with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they blend standard therapies in potentially more effective ways. While lenalidomide and dexamethasone are standard, adding bortezomib introduces a unique element. Bortezomib works by inhibiting proteasomes, which help cancer cells recycle proteins, potentially making the combination more effective at killing cancer cells. This combination could improve outcomes by attacking the cancer in multiple ways, offering hope for better control of the disease.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will compare two treatment regimens for multiple myeloma. Research has shown that the combination of lenalidomide, bortezomib, and dexamethasone effectively treats newly diagnosed multiple myeloma. Participants in one arm of this trial will receive dexamethasone and lenalidomide, while those in another arm will receive dexamethasone, lenalidomide, and bortezomib. Studies have found that the combination including bortezomib is well-tolerated by patients and greatly improves their health outcomes. Lenalidomide helps the immune system attack cancer cells, while bortezomib inhibits the enzymes that cancer cells need to grow. Dexamethasone, a type of chemotherapy, aids by killing cancer cells or stopping their spread. This treatment is widely used and has shown positive results in real-world situations. ^{1 2 5 6 7}

Who Is on the Research Team?

Brian M Durie

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who haven't had treatment before. They need to have enough healthy blood cells, no serious heart conditions, infections or other health issues that could interfere with the study. Women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional federal guidelines

I can take care of myself, but I might not be able to do heavy physical work.

I do not have severe heart issues, recent heart attack, uncontrolled infections, high blood pressure, or diabetes.

Exclusion Criteria

My bone marrow is heavily affected by cancer, with over half of the cells being cancerous.

My multiple myeloma does not produce detectable markers, but my serum Freelite levels are high.

I do not have a performance status of 3 due to other health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive induction therapy with dexamethasone and lenalidomide, with or without bortezomib, depending on the treatment arm

24-32 weeks

Multiple visits as per treatment schedule

Maintenance Therapy

Patients receive maintenance therapy comprising dexamethasone and lenalidomide

Ongoing until disease progression or unacceptable toxicity

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Dexamethasone
• Lenalidomide

Trial Overview

The study compares two treatments: one group receives Lenalidomide and Dexamethasone; another gets these plus Bortezomib. It aims to find out which combination is more effective in stopping cancer growth by either killing cells or preventing them from dividing.

How Is the Trial Designed?

Group I: Arm II (dexamethasone, lenalidomide, bortezomib) Experimental Treatment 4 Interventions

Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (dexamethasone and lenalidomide) Active Control 3 Interventions

Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., 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]

In a phase III study involving 155 multiple myeloma patients, bortezomib and lenalidomide treatments showed similar effectiveness, with 15% and 18% of patients achieving a very good partial response (VGPR) respectively, indicating comparable efficacy.

Both treatment regimens resulted in similar median progression-free survival (PFS) of 16.3 months for bortezomib and 18.6 months for lenalidomide, along with comparable two-year overall survival rates of 75% and 74%, confirming their safety and effectiveness in managing multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. Montefusco, V., Corso, A., Galli, M., et al.[2020]

In two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

Thalidomide, when used as a first-line treatment combined with conventional chemotherapy, has been shown to improve survival rates in patients over 65, despite its potential toxicity to the peripheral nervous system.

Bortezomib and lenalidomide, both effective in treating myeloma relapse, can be used in combination with dexamethasone and each other, indicating a shift towards using these agents to manage myeloma as a chronic disease rather than relying solely on traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. Moreau, P.[2019]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

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Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.

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Lenalidomide (revlimid), bortezomib (velcade) and dexamethasone for heavily pretreated relapsed or refractory multiple myeloma. Leuk Lymphoma. 2012; 54( 3): ...

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Velcade (Bortezomib) & Multiple Myeloma Treatment | IMF

Velcade® (bortezomib) is an injectable anti-cancer agent used in various stages of multiple myeloma. See potential side effects and other information.

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Lenalidomide-bortezomib-dexamethasone resulted in partial response or better in nearly two-thirds of relapsed/refractory myeloma patients.

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Safety and Efficacy of Novel Combination Therapy with ...

These results represent the first clinical data with this novel 4-drug combination that includes bortezomib, lenalidomide, an alkylator, and a corticosteroid.