Daratumumab + Lenalidomide for Multiple Myeloma

(AURIGA Trial)

Not currently recruiting at 92 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with newly diagnosed multiple myeloma, a type of blood cancer. Researchers aim to determine if adding daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) to lenalidomide (also known as Revlimid) can more effectively reduce cancer cells compared to lenalidomide alone. Participants should have undergone multiple myeloma treatments, such as stem cell transplants, and still have detectable cancer cells. The trial seeks individuals who have not previously tried daratumumab and have not experienced certain other health conditions or treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that the combination of daratumumab and lenalidomide has been tested for safety in people with multiple myeloma, a type of blood cancer. When used together, daratumumab and lenalidomide perform as well as the intravenous form of daratumumab. Previous studies indicate that this combination can cause some blood-related side effects, but these are usually manageable and common with multiple myeloma treatments.

Lenalidomide is also commonly used alone to treat multiple myeloma and has received FDA approval, indicating its safety is well-documented for this condition. Like many cancer treatments, lenalidomide can cause side effects, but it is generally safe when monitored by a healthcare professional.

Overall, both daratumumab and lenalidomide have been thoroughly studied, and their safety is well-understood. Researchers closely monitor participants in trials like this one to manage any side effects that may occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the combination of daratumumab and lenalidomide for treating multiple myeloma because it introduces a novel approach to maintenance therapy. While standard treatments often rely on drugs like bortezomib and thalidomide, this combination utilizes daratumumab, a monoclonal antibody that targets CD38 on myeloma cells, enhancing the immune system's ability to fight the cancer. Additionally, daratumumab is administered subcutaneously, which can be more convenient and potentially less time-consuming than traditional intravenous methods. This innovative combo aims to provide more effective and potentially longer-lasting results for patients with multiple myeloma.

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

In this trial, participants will receive either lenalidomide alone or a combination of daratumumab and lenalidomide. Research has shown that combining daratumumab and lenalidomide is promising for treating multiple myeloma, a type of blood cancer. One study found that adding daratumumab to lenalidomide and another drug led to better results and stronger responses in patients. Daratumumab targets a specific protein on cancer cells, helping to achieve minimal residual disease (MRD) negativity. Patients treated with this combination have experienced longer periods without cancer progression. Overall, evidence suggests that adding daratumumab to lenalidomide can enhance treatment effectiveness for multiple myeloma. ^{2 4 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

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Clinical Results A study confirmed the effectiveness of DARZALEX FASPRO ® when used in combination with lenalidomide + dexamethasone (Rd) for relapsed or refractory multiple ...

2. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10507479/

Real-world Duration of Use and Dosing Frequency ... Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as a combination therapy for newly diagnosed multiple myeloma (MM) and as ...

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