DARA-RVD for Smoldering Multiple Myeloma

(PRISM Trial)

Recruiting at 6 trial locations

Overseen By Omar Nadeem, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Omar Nadeem, MD

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: Symptomatic myeloma, Active infection, 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: 24 months

61 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to learn whether the combination of daratumumab SC ( Darzalex Faspro), lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone works in treating smoldering multiple myeloma and preventing progression to active or symptomatic multiple myeloma. The names of the study drugs involved in this study are: * Daratumumab (also called Darzalex Faspro) * Bortezomib (also called Velcade) * Lenalidomide (also called Revlimid) * Dexamethasone

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, it mentions that other concurrent chemotherapy, immunotherapy, or investigational therapies are not allowed, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination DARA-RVD for Smoldering Multiple Myeloma?

Research shows that adding daratumumab to combinations like lenalidomide, bortezomib, and dexamethasone improves outcomes in multiple myeloma, such as higher response rates and longer progression-free survival, suggesting potential benefits for Smoldering Multiple Myeloma as well. ^{1 2 3 4 5}

Is the DARA-RVD treatment safe for humans?

The DARA-RVD treatment, which includes drugs like daratumumab, lenalidomide, bortezomib, and dexamethasone, has been shown to be generally safe in patients with relapsed/refractory multiple myeloma. Common side effects include low blood cell counts, nerve damage, and infections, but these are considered manageable. ^{2 6 7 8 9}

What makes the DARA-RVD drug unique for treating smoldering multiple myeloma?

The DARA-RVD drug combines four different medications—Bortezomib, Daratumumab, Dexamethasone, and Lenalidomide—each with distinct mechanisms to target multiple aspects of smoldering multiple myeloma, potentially offering a more comprehensive approach compared to treatments using fewer components. ^{10 11 12 13 14}

Research Team

Omar Nadeem, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with high-risk smoldering multiple myeloma, who meet specific criteria but do not have active symptoms. Participants must be in good enough health to perform daily activities and agree to birth control measures if applicable. They cannot have had treatment for active myeloma or other cancers within the last two years, among other exclusions.

Inclusion Criteria

Your test results need to be within certain numbers.

I can take care of myself and perform daily activities.

My cancer can be tracked with a specific DNA test for minimal disease.

Exclusion Criteria

You currently have HIV, hepatitis B, hepatitis C, or active COVID-19 infection.

Pregnant or nursing women

I haven't had or been treated for another cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of daratumumab, bortezomib, lenalidomide, and dexamethasone for up to 24 months

24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests a combination of drugs: Daratumumab (Darzalex Faspro), Lenalidomide (Revlimid), Bortezomib (Velcade), and Dexamethasone, on preventing smoldering multiple myeloma from becoming symptomatic. It aims to understand the effectiveness of this drug mix.

Participant Groups

Group I: Daratumumab, Bortezomib,Lenalidomide,Dexamethasone Experimental Treatment 4 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Cycle Length is 28 days. The names of the study drugs involved in this study are: * Daratumumab * Bortezomib * Lenalidomide * Dexamethasone

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?

Omar Nadeem, MD

Lead Sponsor

Trials

3

Recruited

160+

Omar Nadeem

Lead Sponsor

Trials

1

Recruited

60+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE Business School

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

Findings from Research

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]

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 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]

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 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 phase 2 trial and extended access program involving Chinese patients with relapsed/refractory multiple myeloma, lenalidomide plus low-dose dexamethasone (Rd) demonstrated a manageable safety profile, with 60% of patients experiencing Grade 3-4 adverse events, but no patients discontinued treatment due to these adverse effects.

Rd provided sustained efficacy, with a median duration of response of 35.1 months, median time to progression of 36.9 months, and median progression-free survival of 36.0 months, indicating that long-term treatment can be effective for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program. Du, X., Jin, J., Cai, Z., et al.[2018]

Bone metastases in metastatic castration-resistant prostate cancer (mCRPC) significantly impact patient quality of life and are a leading cause of disability and death, highlighting the need for effective management strategies.

Current treatments like zoledronic acid, denosumab, and radium-223 have been shown to reduce skeletal-related events and improve survival, with radium-223 being the first bone-targeting agent to demonstrate improved survival and reduced pain in mCRPC patients without visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting bone metastases in prostate cancer: improving clinical outcome. Body, JJ., Casimiro, S., Costa, L.[2022]

References

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

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

2. 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]

3. 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]

4. United States 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. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]

6. 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]

7. Japan pubmed.ncbi.nlm.nih.gov

Real-world toxicity and effectiveness of ixazomib, lenalidomide, and dexamethasone in Korean patients with relapsed and/or refractory multiple myeloma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program. [2018]

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

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

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

Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma. [2021]

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

The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Therapeutic management of bone metastasis in prostate cancer: an update. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Combination radium-223 therapies in patients with bone metastases from castration-resistant prostate cancer: A review. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Targeting bone metastases in prostate cancer: improving clinical outcome. [2022]