288 Participants Needed

Lenalidomide + Dexamethasone +/- Daratumumab for Multiple Myeloma

Recruiting at 571 trial locations
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

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.12345

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.26789

Who Is on the Research Team?

NS

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.
See 10 more

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?
2Treatment groups
Experimental Treatment
Group I: Arm II (lenalidomide, dexamethasone)Experimental Treatment4 Interventions
Group II: Arm I (daratumumab, lenalidomide, dexamethasone)Experimental Treatment4 Interventions

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

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Approved in European Union as Darzalex for:
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Approved in United States as Darzalex for:

Find a Clinic Near You

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.
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.
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.
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]

Citations

Clinical ResultsA study confirmed the effectiveness of DARZALEX FASPRO ® when used in combination with lenalidomide + dexamethasone (Rd) for relapsed or refractory multiple ...
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.
Real-world Duration of Use and Dosing Frequency ...This real-world analysis reported that the median duration of continuous DARA use is 16.6 months, with high dosing adherence in patients who have MM.
Study Details | NCT04775550 | DARA RVD For High Risk ...This research study is a Phase II clinical trial, which tests the effectiveness of an investigational drug(s). The investigational drugs used in this research ...
FDA approves daratumumab and hyaluronidase-fihj with ...The major efficacy outcome measure was progression-free survival (PFS) as assessed by an independent review committee based on International ...
Daratumumab plus Lenalidomide and Dexamethasone for ...After a median follow-up of 44.3 months, the median progression-free survival was 44.5 months in the daratumumab group, as compared with 17.5 months in the ...
'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 ...
First-Line Treatment Options for Multiple MyelomaThis initial therapy aims to reduce the number of myeloma cells, relieve symptoms, and improve your overall health.
DRVd (Daratumumab + Revlimid® + Velcade® ...DRVd is not given to cure multiple myeloma, but may lead to a complete remission in some patients. DRVd is given to slow the progression of myeloma and to ...
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