Daratumumab + Lenalidomide for Multiple Myeloma

(AURIGA Trial)

Recruiting at 87 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Lenalidomide

Must not be taking: Daratumumab, CD38 therapies

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 36 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding daratumumab to lenalidomide is more effective than using lenalidomide alone for patients with newly diagnosed multiple myeloma. These patients still have detectable cancer cells after initial treatments. Daratumumab helps the immune system find and kill cancer cells, while lenalidomide boosts the immune system and stops cancer growth.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that adding Daratumumab to Lenalidomide and Dexamethasone significantly improves the response rate in patients with multiple myeloma, with more patients achieving a partial response or better compared to those not receiving Daratumumab. ^{1 2 3 4 5}

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

The combination of Daratumumab and Lenalidomide, often used with Dexamethasone, has been shown to be generally safe for treating multiple myeloma, with common side effects including low blood cell counts, nerve damage, and infections. No new safety concerns have been identified in recent studies. ^{1 6 7 8 9}

What makes the drug combination of Daratumumab and Lenalidomide unique for treating multiple myeloma?

This drug combination is unique because it combines Daratumumab, a monoclonal antibody that targets and kills myeloma cells, with Lenalidomide, an immunomodulatory drug, enhancing the immune system's ability to fight the cancer. This combination has shown to improve progression-free survival and overall response rates in patients with multiple myeloma compared to standard treatments. ^{1 3 6 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for individuals with newly diagnosed multiple myeloma who have had at least 4 cycles of induction therapy, a stem cell transplant within the last year, and are still showing minimal residual disease. They should be in relatively good health (ECOG score 0-2) and not have been treated with Daratumumab or similar drugs before.

Inclusion Criteria

I have remaining cancer cells detected by a specific blood test.

I was diagnosed with multiple myeloma, had 4+ treatment cycles, a stem cell transplant within a year of starting treatment, and it's been less than 6 months since my transplant.

I have bone marrow samples or MRD test results from before my treatment.

Exclusion Criteria

You have a known history of testing positive for HIV, hepatitis B, or hepatitis C, unless you have been vaccinated for hepatitis B or have successfully cleared hepatitis C virus from your body.

I have had moderate to severe asthma in the last 2 years or currently have uncontrolled asthma.

I have not had Daratumumab or similar treatments, recent radiation (except for symptom relief), or plasmapheresis in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab plus lenalidomide or lenalidomide alone as maintenance therapy for a maximum of 36 cycles

36 months

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Daratumumab
• Lenalidomide

Trial Overview The study tests if adding Daratumumab to Lenalidomide maintenance treatment helps patients achieve negative status for minimal residual disease compared to using Lenalidomide alone after a stem cell transplant in those who haven't previously received CD38-targeting treatments.

Participant Groups

Group I: Daratumumab + Lenalidomide Experimental Treatment 2 Interventions

Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.

Group II: Lenalidomide Active Control 1 Intervention

Participants will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.

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

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

The combination therapy of carfilzomib, lenalidomide, dexamethasone, and daratumumab achieved a high minimal residual disease (MRD) negativity rate of 71% in newly diagnosed multiple myeloma patients, indicating effective treatment without the need for high-dose melphalan chemotherapy or autologous transplant.

The treatment demonstrated excellent safety and tolerability, with a 1-year progression-free survival rate of 98% and no reported deaths, although some patients experienced grade 3 or 4 adverse events like neutropenia and rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. Landgren, O., Hultcrantz, M., Diamond, B., et al.[2022]

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 a real-world study of 240 relapsed/refractory multiple myeloma patients, treatment with daratumumab, lenalidomide, and dexamethasone (Dara-Rd) resulted in a significantly higher overall response rate (91.2%) compared to lenalidomide and dexamethasone (Rd) alone (69.9%).

Patients receiving Dara-Rd experienced a median progression-free survival (PFS) of 26.9 months, compared to 12.8 months for those on Rd, indicating that Dara-Rd is more effective, especially in patients with fewer prior treatments. However, in patients with more than three previous treatment lines, the benefits of Dara-Rd were not significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma patients - real world evidence analysis. Stork, M., Spicka, I., Radocha, J., et al.[2023]

In a study of 178 multiple myeloma patients who progressed after daratumumab treatment, the median progression-free survival (PFS) was only 4.5 months and overall survival (OS) was 14.2 months, indicating limited effectiveness of subsequent therapies.

Patients receiving pomalidomide-based therapy had a slightly better median PFS and OS (5.2 months and 21.7 months, respectively) compared to those on carfilzomib-based therapy, highlighting the need for new treatment options for patients previously treated with daratumumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. LeBlanc, R., Mian, H., Reece, D., et al.[2023]

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]

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]

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

A systematic review of seven randomized controlled trials involving 4268 patients with multiple myeloma showed that combination regimens containing daratumumab significantly improved overall response rates compared to control groups.

While daratumumab enhanced treatment efficacy in both standard-risk and high-risk patients, it was associated with a higher incidence of severe neutropenia and pneumonia, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis. Wang, Y., Li, Y., Chai, Y.[2021]

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]

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]

References

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

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]

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

Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. [2022]

3. Italy 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. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Daratumumab with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma patients - real world evidence analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. [2023]

6. United States 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. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]

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

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis. [2021]

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

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

11. England 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. [2021]