395 Participants Needed

Daratumumab + VRd for Multiple Myeloma

Recruiting at 153 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Janssen Research & Development, LLC
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial is testing if adding daratumumab to an existing three-drug treatment will improve outcomes for newly diagnosed multiple myeloma patients who are not planning a stem cell transplant. The combination of drugs works together to kill cancer cells in different ways. Daratumumab has shown efficacy in improving overall survival and progression-free survival in multiple myeloma patients when added to other treatment regimens.

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.

What data supports the effectiveness of the drug combination Daratumumab + VRd for treating multiple myeloma?

Research shows that adding daratumumab to the combination of lenalidomide, bortezomib, and dexamethasone improves response rates in patients with newly diagnosed multiple myeloma. Additionally, studies indicate that daratumumab combined with these drugs prolongs the time patients live without the disease getting worse in relapsed or refractory multiple myeloma.12345

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

The combination of Daratumumab with Bortezomib, Lenalidomide, and Dexamethasone has been studied in multiple myeloma patients and is generally considered safe. Common side effects include low blood cell counts (neutropenia, thrombocytopenia, anemia), nerve damage (peripheral sensory neuropathy), and infections.25678

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

This drug combination is unique because it includes Daratumumab, a monoclonal antibody that targets CD38, enhancing the immune system's ability to fight cancer cells, and has shown to significantly prolong progression-free survival in multiple myeloma patients compared to standard treatments. Additionally, the combination therapy has been effective in both newly diagnosed and relapsed/refractory cases, offering a broader treatment option for patients.248910

Research Team

JR

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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
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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.
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Timeline

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

Treatment Details

Interventions

  • Bortezomib
  • Daratumumab
  • Dexamethasone
  • Lenalidomide
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Daratumumab + VRd (D-VRd) and DRdExperimental Treatment4 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 RdActive Control3 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Giacomo Salvadore profile image

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar profile image

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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.
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 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.
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]
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.
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]

References

Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. [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]
Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. [2023]
Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. [2021]
Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. [2023]
Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study. [2022]
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]
Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]
Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]
Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]