Daratumumab + Lenalidomide for Multiple Myeloma

Overseen By Jessica Ellis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must not be taking: Cancer therapy

Disqualifiers: Primary amyloidosis, Waldenström's, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 4

Duration: 16 weeks for initial treatment cycles, followed by ongoing treatment

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of two medications, daratumumab (Darzalex) and lenalidomide, in treating multiple myeloma, a type of blood cancer. Researchers aim to assess how these drugs work together without steroids, which are often used in similar treatments. The trial includes different groups to compare the treatment's effectiveness in patients with varying responses. It seeks participants who have recently been diagnosed with multiple myeloma and have not yet received any treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in multiple myeloma treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are receiving cancer therapy or have had radiation therapy recently, you may not be eligible to participate.

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. Daratumumab, often used with other drugs, can sometimes cause serious reactions affecting the whole body, though these are uncommon. In a large study with 1,249 patients, such reactions were observed, but they do not occur in everyone.

Lenalidomide is usually well-tolerated but can sometimes lead to side effects like low blood counts and tiredness. Both medications are already approved for treating multiple myeloma, providing extensive safety information.

While there are risks, many patients handle these treatments well. Discussing possible side effects and any concerns with a healthcare provider is crucial before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Daratumumab and Lenalidomide for treating multiple myeloma because it brings a new approach to tackling this challenging condition. Most treatments like bortezomib and thalidomide focus on halting cancer cell growth. However, Daratumumab uniquely targets CD38, a protein found on myeloma cells, enhancing the immune system's ability to destroy these cells. When combined with Lenalidomide, which boosts immune function, this duo offers a potentially more effective and comprehensive attack against the cancer, raising hopes for better patient outcomes.

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

Research has shown that using daratumumab and lenalidomide together holds promise for treating multiple myeloma. One study found that 72% of patients experienced progression-free survival over 18 months. The same study reported that 90% of patients were still alive after 18 months, indicating overall survival. Another study demonstrated that adding daratumumab to standard treatment reduced the risk of cancer progression or death by nearly 60%. In this trial, participants will receive different combinations of daratumumab, lenalidomide, and dexamethasone. This combination has achieved an 81% overall response rate, with 63% of patients experiencing a very good partial response or better. These findings suggest that this treatment effectively manages multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Frank Passero, MD

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who haven't had previous treatments and can't have a transplant. They should be able to take oral meds, not be pregnant or breastfeeding, and must not have other severe health issues or recent major surgeries.

Inclusion Criteria

I can take care of myself but cannot do any physical work.

I am a woman who cannot become pregnant because I am either surgically sterile or post-menopausal.

My organs are functioning well.

Exclusion Criteria

I have been diagnosed with a specific blood disorder but it's not active cancer.

I have been diagnosed with Waldenström's disease.

I was diagnosed with cancer less than 2 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, lenalidomide, and dexamethasone. Daratumumab is administered weekly for 8 treatments, then every 2 weeks for 8 treatments, followed by every 4 weeks. Lenalidomide is given daily on days 1-21 of a 28-day cycle.

16 weeks for initial treatment cycles, followed by ongoing treatment

Weekly visits initially, then bi-weekly, then monthly

Response Assessment

Response assessments by International Myeloma Working Group criteria for myeloma will be performed every 4 weeks while on therapy.

Ongoing during treatment

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Lenalidomide

Trial Overview The study tests the effectiveness of daratumumab and lenalidomide without steroids in treating multiple myeloma. It aims to see if patients can avoid steroid-related side effects while still controlling their cancer effectively.

How Is the Trial Designed?

Group I: Experimental Arm: Cycle 5+ Partial Response or Better Experimental Treatment 2 Interventions

Subjects will be treated the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams/kilograms daily days 1-21 out of a 28 day cycle

Group II: Experimental Arm: Cycle 1-4 All subjects Active Control 3 Interventions

Subjects will be treated with the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle * Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab

Group III: Experimental Arm: Cycle 5+ Less than Partial Response Active Control 3 Interventions

Subjects will be treated the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle * Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab

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?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

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]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

A review of 94 safety reports on erenumab, galcanezumab, and fremanezumab found no significant increase in spontaneous abortion or major birth defects, suggesting these medications may be relatively safe during pregnancy and lactation.

Despite the lack of strong evidence for maternal toxicities or adverse outcomes, the limited number of reports and absence of long-term safety data indicate that ongoing monitoring of these drugs in pregnant and lactating women is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database. Noseda, R., Bedussi, F., Gobbi, C., et al.[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]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

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]

In a study involving 401 rheumatoid arthritis patients over a mean follow-up of 70 weeks, rituximab treatment led to a significant reduction in disease activity, as measured by the DAS28-ESR score, from 6.0 at baseline to 4.2 at week 16.

Retreatment with rituximab was more effective when administered before patients showed significant disease flare, indicating that earlier intervention could optimize treatment outcomes for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization of rituximab treatment strategies. Vander Cruyssen, B., Durez, P., Westhovens, R., 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]

In a study of 162 multiple myeloma patients who received daratumumab, combining it with lenalidomide (DRd) showed no significant difference in progression-free survival (PFS) compared to combining it with pomalidomide (DPd) for those previously treated with lenalidomide.

Both treatment combinations (DRd and DPd) were found to be effective options for patients with relapsed/refractory multiple myeloma, indicating that daratumumab with lenalidomide remains a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. Alhaj Moustafa, M., Parrondo, R., Abdulazeez, MF., 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]

Citations

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Daratumumab, Lenalidomide, and Dexamethasone for ... At 18 months, the rate of progression-free survival was 72%, and the rate of overall survival was 90%. ... Here we report the results of a ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/multiple-myeloma-darzalex-plus-vrd

Daratumumab Plus Standard Therapy for Multiple Myeloma Adding daratumumab to the standard treatment resulted in a nearly 60% drop in the risk of cancer progression or death (hazard ratio of 0.42), ...

3. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/newsroom/new-long-term-progression-free-survival-data-projections-reinforce-subcutaneous-darzalex-daratumumab-quadruplet-therapy-as-a-foundational-standard-of-care-for-patients-with-newly-diagnosed-multiple-myeloma

New long-term progression free survival data projections ... Median progression free survival projected to be 17 years for transplant eligible patients receiving daratumumab-based regimen.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5054695/

Phase 1/2 study of daratumumab, lenalidomide, and ... Daratumumab plus lenalidomide/dexamethasone elicited an overall response rate of 81% (63% very good partial response or better).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02252172

NCT02252172 | Study Comparing Daratumumab, ... The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/darzalex-darzalex-faspro-adverse-event-hematologic-events-in-patients-with-newly-diagnosed-multip

Adverse Event - DARZALEX FASPRO® A summary of safety data regarding the occurrence of hematologic events in patients receiving DARZALEX® (daratumumab) and DARZALEX FASPRO® ...

7. darzalexhcp.com darzalexhcp.com/frontline-dvrd/

Frontline DVRd Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Systemic Reactions. In a pooled safety population of 1249 ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.gov Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO [see. Adverse Reactions (6.3)]. Systemic Reactions. In a ...

9. 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.

10. darzalex.com darzalex.com/clinical-results/

Clinical Results A study confirmed that DARZALEX FASPRO ® gave patients results comparable to the IV formulation of DARZALEX ® in treating multiple myeloma when used by itself.