DARA-RVD for Smoldering Multiple Myeloma

(PRISM Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of four drugs—daratumumab, bortezomib, lenalidomide, and dexamethasone—can effectively treat smoldering multiple myeloma and prevent its progression into a more serious form. Smoldering multiple myeloma represents an early stage of cancer that hasn't yet caused symptoms or damage but has the potential to become active. Suitable candidates for this trial should have a diagnosis of high-risk smoldering multiple myeloma, indicating certain features that could lead to full-blown multiple myeloma. 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 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.

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

Research has shown that a combination of four drugs—daratumumab, bortezomib, lenalidomide, and dexamethasone—treats multiple myeloma. The FDA has approved this treatment, indicating thorough study. Reports indicate that while 92% of patients may experience some side effects, only 18% face serious blood-related issues. Most people handle the treatment well, but some risks exist. Discuss these risks with your doctor when considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for smoldering multiple myeloma because it brings together a unique mix of treatments that target the disease in different ways. Daratumumab is a monoclonal antibody that targets a specific protein on myeloma cells, enhancing the immune system's ability to destroy them. Bortezomib disrupts the cancer cells' protein recycling process, leading to cell death, while Lenalidomide boosts immune function and Dexamethasone reduces inflammation. This multi-faceted approach could potentially be more effective than current treatments, which often use these drugs individually, and may slow disease progression more effectively.

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

Research has shown that a combination of four drugs—daratumumab, bortezomib, lenalidomide, and dexamethasone—can be promising in treating multiple myeloma. This combination, known as DARA-RVD, is being studied in this trial for its potential to slow high-risk smoldering multiple myeloma before it becomes active. In previous studies, patients who received this combination had much better results than those who did not. The combination attacks cancer cells in different ways, making it a strong option for managing the disease. The approval and positive outcomes in past patients suggest it could effectively treat smoldering multiple myeloma. ^{1 2 3 6 7}

Who Is on the Research Team?

Omar Nadeem, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1.

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 ...

2.

jnj.com

jnj.com/media-center/press-releases/european-commission-approves-darzalex-daratumumab-as-the-first-licensed-treatment-for-patients-with-high-risk-smouldering-multiple-myeloma

European Commission approves DARZALEX® ...

European Commission approves DARZALEX® (daratumumab) as the first licensed treatment for patients with high-risk smouldering multiple myeloma.

3.

aetna.com

aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ...

Darzalex Faspro is indicated for the treatment of adult patients with multiple myeloma: in combination with bortezomib, lenalidomide, and dexamethasone for ...

4.

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 ...

A total of 709 patients were randomized: 355 to the Darzalex Faspro with bortezomib, lenalidomide, and dexamethasone (Darzalex Faspro-VRd) arm ...

5.

oncologypipeline.com

oncologypipeline.com/apexonco/jj-claims-tecvaylidarzalex-combo-win

J&J claims a Tecvayli/Darzalex combo win | ApexOnco

In the study Tecvayli and Darzalex Faspro were pitted against Darzalex with dexamethasone, plus either Pomalyst or Velcade. J&J, which ...

6.

myeloma.org

myeloma.org/darzalex-daratumumab

Darzalex (Daratumumab)

Darzalex (daratumumab) is a highly effective drug used to treat multiple myeloma. Read about who is a candidate, side effects, special warnings.

7.

jnjmedicalconnect.com

jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-darzalex-faspro-use-in-smoldering-multiple-myeloma

darzalex - Use in Smoldering Multiple Myeloma

Any grade toxicity possibly related to treatment occurred in 92% of patients, grade ≥3 hematological toxicities occurred in 18% of patients and non- ...