Lenalidomide + Dexamethasone +/- Thalidomide for Multiple Myeloma

Recruiting at 158 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: 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

Compensation: Varies

Number of Visits: 7

Duration: 16 weeks

452 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different drug combinations, specifically lenalidomide (Revlimid), dexamethasone (Decadron), and thalidomide (Thalomid), in treating multiple myeloma, a type of blood cancer. Researchers seek to determine if these medications can halt cancer growth by killing cancer cells or blocking their blood supply. Participants will receive varying doses and combinations of these drugs to identify the most effective treatment. Individuals diagnosed with symptomatic multiple myeloma within the last 90 days who have not received prior systemic treatment may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that lenalidomide and dexamethasone are usually well-tolerated by patients with multiple myeloma. However, some risks exist. Studies have found a higher chance of developing blood clots in the arteries, veins, or lungs when taking lenalidomide with dexamethasone. This risk is greater for patients with multiple myeloma.

The safety of thalidomide and dexamethasone has also been studied. Thalidomide can increase the risk of blood clots, but using a lower dose has proven safer.

Both treatment combinations have been extensively studied, providing a good understanding of their safety. While risks are present, these treatments have been part of many studies, which help in managing side effects effectively. Always discuss these risks and any concerns with your doctor. ^{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 explore unique combinations of drugs that could improve patient outcomes. Unlike standard therapies, which often rely on single agents or fixed combinations, this approach combines lenalidomide and dexamethasone with or without thalidomide. Lenalidomide and thalidomide are both immunomodulatory drugs, but lenalidomide is known for having a more favorable side effect profile, potentially increasing tolerability. Additionally, combining these drugs with dexamethasone, a steroid that reduces inflammation, may enhance their efficacy by targeting the cancer cells more effectively. This trial could lead to more personalized and effective treatment strategies for patients with multiple myeloma.

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

Research has shown that using lenalidomide with dexamethasone, one of the treatment combinations in this trial, can help treat multiple myeloma. In one study, 32% of patients experienced significant shrinkage or disappearance of their cancer. Another study found that 24 to 29% of patients with hard-to-treat multiple myeloma saw a reduction in their cancer, though it didn't vanish completely.

For participants receiving the combination of thalidomide and dexamethasone, studies indicate that about 30% of patients with recurring or stubborn multiple myeloma responded well, with some experiencing complete disappearance of their cancer. Both treatment combinations in this trial have shown promise in managing the condition by effectively targeting cancer cells. ^{4 6 7 8 9}

Who Is on the Research Team?

S. V Rajkumar

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

Must meet specified hematologic parameters including hemoglobin, platelet count, and absolute neutrophil count

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2503648/

A review of lenalidomide in combination with ... Thirty-one of 34 patients achieved an objective response, including 2 (6%) achieving complete response (CR) and 11 (32%) meeting criteria for both very good ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9972020/

Real‐world data on lenalidomide dosing and outcomes in ... All patients received lenalidomide 5–25 mg mostly on days 1–21 and dexamethasone 8 – 40 mg on a once weekly schedule (subsequent dexamethasone ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0147027224000199

An analysis of real-world electronic health records data Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa070596

Lenalidomide plus Dexamethasone for Relapsed Multiple ... Phase 1 and 2 trials of lenalidomide in patients with treatment-refractory multiple myeloma showed a partial-response rate of 24 to 29%. Moreover, an additional ...

5. haematologica.org haematologica.org/article/view/5759

Better quality of response to lenalidomide plus ... Among the 353 patients treated with lenalidomide plus dexamethasone in these clinical trials, 114 (32.3%) achieved a CR/VGPR and 100 (28.3%) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2728892/

Expanded safety experience with lenalidomide plus ... Primary cause of death was disease progression (10%). Safety data confirmed known AEs of lenalidomide plus dexamethasone therapy in patients with relapsed/ ...

7. myeloma.org myeloma.org/revlimid-lenalidomide

Revlimid (Lenalidomide) For patients taking the combination of Revlimid and dexamethasone, the Boxed Warnings include an increased risk of arterial and venous thromboembolism (VTE, ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-cancer-drug-revlimid-lenalidomide-and-risk

Safety review update of cancer drug Revlimid Know that, in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of ...

9. revlimid.com revlimid.com/

REVLIMID® (lenalidomide) - Official Patient Website Blood clots in the arteries, veins, and lungs happen more often in people who take REVLIMID. This risk is even higher for people with multiple myeloma who take ...