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

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in subjects with newly diagnosed multiple myeloma (NDMM) who are eligible for standard-of-care autologous stem cell transplantation (ASCT). Daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) have recently become a standard induction regimen for patients with NDMM who are eligible for ASCT in the United States. As implemented in clinical trials, Dara-RVd involves twice weekly bortezomib administration, which is inconvenient for patients and may result in increased rates of limiting toxicity, such as peripheral neuropathy. Adoption of alternate schedules involving once-weekly bortezomib is common in real-world practice, however a paucity of prospective data supporting this practice exists. This study examines the efficacy of an attenuated Dara-RVd schedule involving once-weekly bortezomib dosing.

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.

What data supports the effectiveness of the drug combination Dara-RVd for treating multiple myeloma?

Research shows that combining daratumumab with other drugs like lenalidomide, bortezomib, and dexamethasone significantly improves outcomes for patients with multiple myeloma, including longer periods without disease progression and higher response rates. ^{1 2 3 4 5}

Is the Dara-RVd treatment safe for humans?

The combination of daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) has been shown to be generally safe in patients with multiple myeloma, with common side effects including low blood cell counts, nerve damage, and infections. ^{1 4 6 7 8}

What makes the Dara-RVd drug unique for treating multiple myeloma?

The Dara-RVd drug is unique because it combines daratumumab, a monoclonal antibody that targets cancer cells, with the standard RVD regimen (lenalidomide, bortezomib, and dexamethasone), enhancing the complete response rate in newly diagnosed multiple myeloma patients eligible for transplantation. ^{1 2 3 6 9}

Research Team

Samuel M Rubinstein, MD, MSCI

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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.

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 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]

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 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 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 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]

References

1. United States 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. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Daratumumab-based Triplet Therapies in Patients With Relapsed or Refractory Multiple Myeloma. [2019]

4. United States 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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]

7. United States pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for heavily pretreated relapsed or refractory multiple myeloma. [2019]

9. United States 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. [2023]