Daratumumab + VRd for Multiple Myeloma

Not currently recruiting at 184 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Frailty, Prior therapy, Invasive malignancy, 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

Compensation: Varies

Number of Visits: 1

Duration: Approximately 2.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding daratumumab, a monoclonal antibody, to the usual treatment of bortezomib, lenalidomide, and dexamethasone can more effectively treat multiple myeloma, a type of blood cancer. Researchers aim to determine if this combination reduces cancer cells more effectively than the standard treatment alone. The study targets individuals diagnosed with multiple myeloma who have measurable disease and have not undergone extensive prior treatment. 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 does not specify if you need to stop taking your current medications. However, it mentions that prior therapy for multiple myeloma, other than a short course of corticosteroids, is not allowed. It's best to discuss your current medications with the trial team.

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

Research shows that adding daratumumab to the combination of bortezomib, lenalidomide, and dexamethasone (VRd) is generally safe for patients with multiple myeloma. Previous studies have found this combination promising in terms of safety.

The FDA has approved daratumumab with these drugs for treating multiple myeloma, indicating its safety for patients. This approval confirms that the treatment has been tested and deemed safe for individuals with this condition.

Reported side effects of this combination include tiredness, nausea, and low blood counts, but medical help can manage these. While some patients may experience these side effects, others may not. Earlier studies provide strong evidence of the treatment's safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Daratumumab with VRd (Bortezomib, Lenalidomide, and Dexamethasone) for treating multiple myeloma because it introduces a new layer of action by targeting a specific protein called CD38 on myeloma cells. While standard treatments like VRd focus on disrupting cancer cell growth and survival, Daratumumab adds a unique mechanism by enhancing the immune system's ability to identify and destroy these cells. This combined approach not only bolsters the effectiveness of the existing regimen but also has the potential to improve outcomes in patients with this challenging condition.

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

In this trial, participants will receive different treatment combinations for multiple myeloma. Research has shown that adding daratumumab to the usual VRd treatment (which includes bortezomib, lenalidomide, and dexamethasone) can lead to better patient outcomes. Studies have found that this combination helps patients live longer without their cancer worsening. Specifically, previous research data revealed that patients who received the D-VRd combination had higher survival rates compared to those who received only VRd. Daratumumab targets a specific protein on cancer cells, enhancing the immune system's ability to fight the cancer. This suggests that the D-VRd combination could be a more effective treatment option for multiple myeloma. ^{1 3 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 adults with untreated multiple myeloma who don't plan to have a stem cell transplant right away. They must have measurable disease, be able to perform daily activities (ECOG score 0-2), and women of childbearing age need two negative pregnancy tests before dosing. People can't join if they've had other cancer treatments or certain health conditions like severe neuropathy.

Inclusion Criteria

You must have a way for doctors to measure your disease using tests from a central laboratory.

A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing

A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen

Exclusion Criteria

I have moderate to severe nerve pain or damage.

I have only used a short course of corticosteroids for my multiple myeloma.

I haven't had cancer, except for certain skin cancers or early-stage cervical or breast cancer, in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd) or bortezomib, lenalidomide, and dexamethasone (VRd) until disease progression or unacceptable toxicity

Approximately 2.5 years

Weekly visits for Cycles 1-2, every 3 weeks for Cycles 3-8, and every 4 weeks for Cycle 9 and beyond

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study is testing whether adding Daratumumab to the combination of Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) improves outcomes compared to just VRd in treating multiple myeloma. The main goal is seeing if this mix reduces the number of remaining cancer cells better than the standard combo.

How Is the Trial Designed?

Group I: Daratumumab + VRd (D-VRd) and DRd Experimental Treatment 4 Interventions

Participants will receive daratumumab 1800 mg as SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3 through 8 and every 4 weeks for Cycle 9 and beyond; bortezomib 1.3 mg/m\^2 as SC injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9; dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond followed by daratumumab-lenalidomide-dexamethasone (DRd) until disease progression or unacceptable toxicity.

Group II: Bortezomib + Lenalidomide + Dexamethasone (VRd) and Rd Active Control 3 Interventions

Participants will receive bortezomib 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 (cycle of 28 days); dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond (each cycle is of 28 days) followed by lenalidomide-dexamethasone (Rd) until disease progression or unacceptable toxicity.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell 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

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]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Facon, T., Kumar, S., Plesner, T., et al.[2023]

In the final analysis of the CASTOR study, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma, with a median OS of 49.6 months compared to 38.5 months for bortezomib and dexamethasone alone (Vd).

The study, which followed patients for a median of 72.6 months, found that D-Vd provided OS benefits across various subgroups, including older patients and those with high-risk disease, although it was associated with higher rates of certain adverse events like thrombocytopenia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. Sonneveld, P., Chanan-Khan, A., Weisel, K., et al.[2023]

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 the phase 3 LEPUS study involving 211 Chinese patients with relapsed or refractory multiple myeloma, the combination of daratumumab, bortezomib, and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) compared to bortezomib and dexamethasone alone (median PFS of 14.8 months vs. 6.3 months).

D-Vd also showed higher overall response rates and better response quality, with 84.7% of patients achieving an overall response compared to 66.7% with Vd, and no new safety concerns were identified, supporting D-Vd as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. Fu, W., Li, W., Hu, J., 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]

Citations

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Daratumumab plus bortezomib, lenalidomide and ... Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04775550

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 ...

3. nature.com nature.com/articles/s41408-024-01120-9

Quadruplet therapy for newly diagnosed myeloma The combination of lenalidomide, bortezomib, and dexamethasone (RVd) was shown to be highly effective in newly diagnosed myeloma (NDMM) patients ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients

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

Daratumumab Plus Standard Therapy for Multiple Myeloma Adding daratumumab (Darzalex) to standard VRD treatment helped people with newly diagnosed multiple myeloma live longer without their cancer ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-multiple

FDA approves daratumumab and hyaluronidase-fihj with ... FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma · Efficacy and Safety.

7. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/fda-daratumumab-isatuximab-newly-diagnosed-myeloma

Darzalex Faspro, Sarclisa Approvals for Multiple Myeloma Two recent approvals by the Food and Drug Administration (FDA) broaden the initial treatment options for people who have a new diagnosis of multiple myeloma.

8. 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.