Dara-RVd for Multiple Myeloma

Overseen By Ralph L Dessieu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Daratumumab, Lenalidomide, Bortezomib, Dexamethasone

Disqualifiers: Active infection, Pregnancy, Breastfeeding, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new schedule for a treatment called Dara-RVd to determine its effectiveness for individuals with newly diagnosed multiple myeloma, a type of blood cancer. The standard treatment involves frequent doses of bortezomib (also known as Velcade), which can be inconvenient and potentially harmful. This trial tests administering bortezomib just once a week instead. It suits individuals with newly diagnosed multiple myeloma who are eligible for a stem cell transplant and can adhere to the trial's procedures. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 team 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 four drugs—daratumumab, lenalidomide, bortezomib, and dexamethasone, known as Dara-RVd—is generally safe for people with multiple myeloma. The FDA has approved this combination for newly diagnosed patients.

While these drugs can be effective, they may also cause side effects. Common side effects include fatigue, nausea, and an increased risk of infections. One study found that using bortezomib less frequently, such as once a week instead of twice, might help reduce side effects like nerve pain in the hands or feet.

Overall, most people tolerate the treatment well, but patients should discuss possible side effects and management strategies with their doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Dara-RVd treatment for multiple myeloma because it combines four powerful drugs: daratumumab, lenalidomide, bortezomib, and dexamethasone. This combination is unique because daratumumab is a monoclonal antibody that targets a specific protein on myeloma cells, enhancing the immune system's ability to destroy them. Additionally, when combined with the other drugs, which have different mechanisms of action, it offers a comprehensive approach that could improve outcomes compared to standard treatments, which often include just one or two of these drugs. This multi-drug regimen aims to tackle the cancer from multiple angles, potentially leading to better results for patients.

What is the effectiveness track record for the Dara-RVd treatment in newly diagnosed multiple myeloma?

Studies have shown that a treatment combining four drugs—daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd)—works well for patients with newly diagnosed multiple myeloma who can undergo a stem cell transplant. The FDA has approved this treatment, and it has significantly improved patient outcomes. Specifically, research indicates a 60.9% improvement in reducing cancer cells and a 43% increase in patient response to the treatment. This combination is widely accepted as a strong option for treating this type of cancer. In this trial, researchers are also exploring the possibility of administering bortezomib once a week, as it might reduce side effects like nerve pain without compromising effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Samuel M Rubinstein, MD, MSCI

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed multiple myeloma who are fit enough for a stem cell transplant. Participants must be able to follow the study's procedures and not have any serious infections or be pregnant/breastfeeding.

Inclusion Criteria

I have been diagnosed with Multiple Myeloma.

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information

Subjects willing and able to comply with study procedures based on the judgment of the investigator

Exclusion Criteria

Pregnant or breastfeeding

I haven't had a serious infection or needed antibiotics in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) with an attenuated schedule involving once-weekly bortezomib dosing

8 weeks

Stem Cell Transplantation

Participants undergo standard-of-care autologous stem cell transplantation (ASCT)

60 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The trial tests a less frequent dosing schedule of Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (Dara-RVd) in patients eligible for autologous stem cell transplantation. It aims to see if taking Bortezomib once weekly instead of twice reduces side effects while remaining effective.

How Is the Trial Designed?

Group I: Daratumumab, lenalidomide, bortezomib, and dexamethasone Experimental Treatment 4 Interventions

Subjects with newly diagnosed multiple myeloma (NDMM) are eligible for standard-of-care autologous stem cell transplantation (ASCT) and receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd).

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

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 a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

In a study of 1,000 newly diagnosed myeloma patients treated with the RVD induction regimen, an impressive overall response rate of 97.1% was observed, with 89.9% achieving a very good partial response or better after transplantation.

The median overall survival for the entire cohort was 126.6 months, with 10-year survival rates of 29% for high-risk patients and 58% for standard-risk patients, highlighting the long-term benefits of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma. Joseph, NS., Kaufman, JL., Dhodapkar, MV., et al.[2021]

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]

The addition of daratumumab to bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) for treating relapsed or refractory multiple myeloma was shown to be effective, but the cost-effectiveness of these combinations is questionable due to high costs.

The incremental cost-effectiveness ratio (ICER) for DVd was $284,180 per quality-adjusted life year (QALY) and for DRd was $1,369,062 per QALY, indicating that significant price reductions for daratumumab would be necessary for these treatments to be considered cost-effective in the US healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Daratumumab-based Triplet Therapies in Patients With Relapsed or Refractory Multiple Myeloma. Zhang, TT., Wang, S., Wan, N., et al.[2019]

In a phase II study involving 31 patients under 65 years old with newly diagnosed multiple myeloma, the combination therapy of lenalidomide, bortezomib, and dexamethasone (RVD) led to high response rates, with 87% of patients achieving a very good partial response or better after consolidation therapy.

The treatment showed favorable safety, with no treatment-related mortality and a 100% overall survival rate at 3 years; importantly, 68% of patients achieved minimal residual disease (MRD) negativity, and none of these patients relapsed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. Roussel, M., Lauwers-Cances, V., Robillard, N., et al.[2022]

Citations

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DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

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

Study Details | NCT04775550 | DARA RVD For High Risk ... The purpose of this research study is to learn whether the combination of daratumumab SC ( Darzalex Faspro), lenalidomide (Revlimid), bortezomib (Velcade) ...

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

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DARZALEX FASPRO®-based quadruplet regimen ... Study of the first and only subcutaneous quadruplet regimen demonstrates 60.9 percent improvement in minimal residual disease (MRD)-negativity and 43 percent ...

5. jheor.org jheor.org/article/141714-cost-of-anti-cd38-monoclonal-antibodies-in-combination-with-bortezomib-lenalidomide-and-dexamethasone-for-the-frontline-treatment-of-transplant-ineli

Cost of Anti-CD38 Monoclonal Antibodies in Combination ... The efficacy of the combination of bortezomib, lenalidomide, and dexamethasone with daratumumab (DVRd) or isatuximab (IsaVRd) for the frontline ...

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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. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimens-demonstrate-improved-rates-of-minimal-residual-disease-mrd-negativity-and-progression-free-survival-in-patients-with-newly-diagnosed-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase ... New analysis from Phase 3 CEPHEUS study demonstrates 85 percent of patients who achieved MRD negativity (10-6) with DARZALEX FASPRO® were ...