~131 spots leftby Dec 2029

Lenalidomide + Dexamethasone +/- Daratumumab for Multiple Myeloma

Recruiting at 557 trial locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: ECOG-ACRIN Cancer Research Group
Must not be taking: Erythropoietin, Glucocorticosteroids
Disqualifiers: Seizure disorder, Hypertension, Heart failure, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide and dexamethasone with daratumumab may work better in treating patients with smoldering myeloma.

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.

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

Research shows that adding Daratumumab to Lenalidomide and Dexamethasone significantly improves outcomes for multiple myeloma patients. In studies, this combination reduced the risk of disease progression or death and increased the number of patients who responded well to treatment compared to using Lenalidomide and Dexamethasone alone.12345

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

The combination of Lenalidomide, Dexamethasone, and Daratumumab has been generally well-tolerated in multiple myeloma patients, with common side effects including low blood cell counts (neutropenia, thrombocytopenia, anemia), nerve damage (peripheral sensory neuropathy), and infections. Infusion-related reactions were mostly mild and occurred during the first infusion.13456

How does the drug combination of Lenalidomide, Dexamethasone, and Daratumumab differ from other treatments for multiple myeloma?

The combination of Lenalidomide, Dexamethasone, and Daratumumab is unique because it includes Daratumumab, a monoclonal antibody that targets CD38 on myeloma cells, enhancing the immune system's ability to kill these cells. This combination has shown to significantly improve progression-free survival and overall response rates compared to Lenalidomide and Dexamethasone alone, making it a more effective option for patients with relapsed or refractory multiple myeloma.13467

Research Team

NS

Natalie S Callander

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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 must have a specific urine test monthly if my initial results show a high protein level.
I was diagnosed with a high-risk form of smoldering multiple myeloma less than a year ago and I don't have symptoms.
See 10 more

Trial Timeline

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

Treatment Details

Interventions

  • Daratumumab (Immunotherapy)
  • Dexamethasone (Corticosteroid)
  • Lenalidomide (Immunomodulator)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (lenalidomide, dexamethasone)Experimental Treatment4 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 Treatment4 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.

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+

Findings from Research

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.
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]
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]
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]

References

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]
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. [2021]
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]
Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]
Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]
Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]
Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. [2021]