Lenalidomide + Dexamethasone +/- Daratumumab for Multiple Myeloma

Recruiting at 571 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 27

Duration: 24 months

288 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining lenalidomide and dexamethasone with or without daratumumab is more effective for treating high-risk smoldering multiple myeloma. The researchers aim to determine if adding daratumumab, an immunotherapy drug, can more effectively halt the growth and spread of cancer cells. Suitable participants have received a diagnosis of high-risk smoldering multiple myeloma within the past year and exhibit specific disease markers, such as certain protein levels or genetic features, but do not yet show symptoms. As a Phase 3 trial, this study 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 does not specify if you need to stop taking your current medications. However, you cannot have had prior or concurrent systemic or radiation therapy for myeloma, and certain medications like erythropoietin and high-dose glucocorticosteroids are not allowed during the study.

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

A previous study showed that patients treated with lenalidomide and dexamethasone had a response rate of about 50% and experienced generally manageable side effects. Most patients tolerated this combination well, with an average survival time of around three years.

When researchers added daratumumab to lenalidomide and dexamethasone, the results were encouraging. Over 90% of patients with newly diagnosed multiple myeloma responded well to the treatment, and the side effects remained mostly manageable.

Overall, these treatments have been well-tolerated, with most side effects being manageable. The safety data from these studies suggest that the treatment options in the trial are relatively safe for participants. ^{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 combine different drugs to potentially enhance effectiveness. Daratumumab is a standout as it’s an antibody that precisely targets the CD38 protein on myeloma cells, marking them for destruction by the immune system. This targeting mechanism differentiates it from traditional chemotherapy, which can affect both healthy and cancerous cells. Meanwhile, lenalidomide and dexamethasone work together to boost the immune system and reduce inflammation. This combination approach could offer improved outcomes by attacking the cancer from multiple angles and is especially promising for patients who have not responded well to existing therapies.

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

Research has shown that a combination of daratumumab, lenalidomide, and dexamethasone, which participants in this trial may receive, effectively treats multiple myeloma. One study found that this combination helps prevent cancer progression for an extended period. Patients using these drugs demonstrated strong and lasting improvements, with many reaching a point where almost no cancer is detectable. Another treatment arm in this trial involves lenalidomide and dexamethasone alone, common and effective treatments for both newly diagnosed and recurrent multiple myeloma. These drugs work by stopping cancer cells from growing and spreading. This provides strong evidence that these treatments effectively fight multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Natalie S Callander

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with high-risk smoldering myeloma diagnosed within the last year. Participants must not have severe heart failure, active infections, or certain other health conditions. They should not be pregnant and must use effective contraception. Prior cancer treatments are disallowed except if it was curative and the patient has been disease-free for a set period.

Inclusion Criteria

I am not pregnant, will test regularly, and use birth control during treatment.

I was diagnosed with a high-risk form of smoldering multiple myeloma less than a year ago and I don't have symptoms.

I must have a specific urine test monthly if my initial results show a high protein level.

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 or without daratumumab. Treatment repeats every 28 days for up to 24 cycles.

24 months

Monthly visits for up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3, 6, or 12 months.

Up to 15 years

Follow-up visits every 3, 6, or 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview

The study tests lenalidomide and dexamethasone with or without daratumumab in patients with high-risk smoldering myeloma. It aims to see if adding daratumumab improves outcomes by altering the immune system's response to tumor cells.

How Is the Trial Designed?

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

Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

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

Patients receive daratumumab IV on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of courses 7-24. Patients also receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 in courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 737 patients with newly diagnosed multiple myeloma, the addition of daratumumab to lenalidomide and dexamethasone significantly reduced the risk of disease progression or death, with a hazard ratio of 0.56, indicating a 44% lower risk compared to the control group.

Patients receiving daratumumab had a higher rate of complete response (47.6% vs. 24.9%) and a greater percentage achieving minimal residual disease status (24.2% vs. 7.3%), although they also experienced more severe side effects like neutropenia and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Facon, T., Kumar, S., Plesner, T., et al.[2023]

In the phase 3 MAIA trial involving 737 patients, the combination of daratumumab, lenalidomide, and dexamethasone significantly improved both progression-free survival (not reached vs. 34.4 months in the control group) and overall survival (hazard ratio 0.68) in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.

The safety profile of the treatment was consistent with previous findings, with no new safety concerns identified, although higher rates of neutropenia and pneumonia were observed in the daratumumab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Facon, T., Kumar, SK., Plesner, T., et al.[2021]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

Daratumumab combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Combining lenalidomide with daratumumab significantly enhances the ability of the immune system to kill multiple myeloma cells, as shown in assays using both cell lines and primary patient cells.

The synergy between lenalidomide and daratumumab was particularly evident in the bone marrow environment of multiple myeloma patients, suggesting that this combination could be a powerful treatment strategy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. van der Veer, MS., de Weers, M., van Kessel, B., et al.[2021]

In the POLLUX study, after 25.4 months of follow-up, the combination of daratumumab with lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma, with a hazard ratio of 0.41 compared to lenalidomide/dexamethasone alone.

The overall response rate was notably higher with the daratumumab combination (92.9%) compared to the control (76.4%), and a significant proportion of patients achieved minimal residual disease negativity (26.2% vs 6.4%), indicating a deeper response without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Dimopoulos, MA., San-Miguel, J., Belch, A., et al.[2019]

Citations

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DARZALEX FASPRO® (daratumumab and hyaluronidase ...

A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

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cancernetwork.com

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'Virtually All Patients' with Newly Diagnosed Transplant ...

More than 90% of patients with newly diagnosed transplant-ineligible multiple myeloma treated with daratumumab plus lenalidomide and dexamethasone will achieve ...

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First-Line Treatment Options for Multiple Myeloma

This initial therapy aims to reduce the number of myeloma cells, relieve symptoms, and improve your overall health.

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