Lenalidomide + Dexamethasone +/- Thalidomide for Multiple Myeloma

Recruiting at 153 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

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: 7

Duration: 16 weeks

452 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if lenalidomide with either standard or low-dose dexamethasone works better for new multiple myeloma patients. If not, thalidomide is added. The goal is to find effective treatments with fewer side effects. Lenalidomide plus low-dose dexamethasone has been shown to be an effective treatment for multiple myeloma, particularly in patients who are not candidates for stem cell transplantation.

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 prior systemic therapy for multiple myeloma is not allowed, except for bisphosphonates. If you are on glucocorticosteroids for non-cancer conditions, you may continue, but the dose should be limited to the equivalent of prednisone 10 mg per day.

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

Research shows that the combination of Lenalidomide and Dexamethasone is effective in treating multiple myeloma, with studies indicating it improves survival and response rates in patients who have relapsed or are resistant to other treatments. In particular, it has been shown to be more effective than Dexamethasone alone and has been approved by the FDA for use in patients who have received prior therapy. ^{1 2 3 4 5}

Is the combination of Lenalidomide, Dexamethasone, and Thalidomide safe for treating multiple myeloma?

The combination of Lenalidomide and Dexamethasone is generally well-tolerated for treating multiple myeloma, but common side effects include fatigue, muscle cramps, rash, infection, and blood-related issues like cytopenias (low blood cell counts). Safety studies have shown that while there are some risks, the treatment is considered safe enough to be approved by health authorities for use in multiple myeloma patients. ^{3 6 7 8 9}

What makes the drug combination of lenalidomide and dexamethasone unique for treating multiple myeloma?

The combination of lenalidomide and dexamethasone is unique because lenalidomide is a more potent version of thalidomide, offering stronger immune system effects, and when used together, they have shown to be more effective than dexamethasone alone in treating relapsed or refractory multiple myeloma, even in patients who have been previously treated with other drugs like thalidomide and bortezomib. ^{1 3 4 10 11}

Research Team

S. V Rajkumar

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults recently diagnosed with symptomatic multiple myeloma. They should have certain blood and marrow conditions, not be pregnant or breastfeeding, and can't have had previous systemic therapy for the disease (except bisphosphonates). People with severe illnesses, uncontrolled infections, a history of blood clots without anticoagulation therapy, or significant neuropathy cannot join.

Inclusion Criteria

I have had cancer before but meet specific conditions for this trial.

I am able to care for myself and perform daily activities.

I was diagnosed with multiple myeloma recently and have symptoms.

Exclusion Criteria

I do not have any serious illnesses that are not under control.

I have never had deep vein thrombosis or a pulmonary embolism.

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

Participants receive lenalidomide and dexamethasone, with cycles repeating every 28 days for up to 4 cycles

16 weeks

Visits every 4 weeks

Salvage Therapy

Non-responders receive thalidomide and dexamethasone, with cycles repeating every 28 days

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

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

Treatment Details

Interventions

• Dexamethasone
• Lenalidomide
• Thalidomide

Trial Overview The study compares lenalidomide combined with low or standard doses of dexamethasone against the same regimen plus thalidomide in treating multiple myeloma. It aims to see which combination is more effective at stopping cancer growth by affecting the immune system and cutting off cancer's blood supply.

Participant Groups

Group I: Arm IV (thalidomide, low-dose dexamethasone) Experimental Treatment 3 Interventions

Patients with no response after treatment on Arm II: Patients receive thalidomide as in arm III and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.

Group II: Arm II (lenalidomide, low-dose dexamethasone) Experimental Treatment 3 Interventions

Patients receive lenalidomide and acetylsalicylic acid as in Arm I and low-dose dexamethasone PO QD on days 1, 8, 15, and 22.

Group III: Arm III (thalidomide, dexamethasone) Active Control 3 Interventions

Patients with no response after treatment on Arm I: Patients receive thalidomide PO QD on days 1-28 and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20

Group IV: Arm I (lenalidomide, dexamethasone) Active Control 3 Interventions

Patients receive lenalidomide PO QD on days 1-21 and standard-dose dexamethasone PO QD on days 1-4, 9-12, and 17-20.

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

In a pooled analysis of two phase III trials involving 704 patients with relapsed or refractory multiple myeloma, lenalidomide combined with dexamethasone significantly improved the overall response rate compared to placebo plus dexamethasone across all age groups.

Lenalidomide plus dexamethasone also prolonged progression-free survival and time-to-progression in all age groups, indicating its efficacy as a treatment option for multiple myeloma, although the overall survival benefit was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ≥65 years old with relapsed or refractory multiple myeloma. Chanan-Khan, AA., Lonial, S., Weber, D., et al.[2021]

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 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]

References

1. England 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. [2018]

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

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

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

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

5. Japan pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ≥65 years old with relapsed or refractory multiple myeloma. [2021]

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

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

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

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. [2021]

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

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

9. China pubmed.ncbi.nlm.nih.gov

[Curative Efficacy of Lenalidomide plus Low Dose Dexamethasone for Multiple Myeloma]. [2018]

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

Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. [2022]

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

Management of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide. [2018]