Quadruple Drug Therapy for Multiple Myeloma

Overseen By Larysa Sanchez

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Larysa Sanchez

Must not be taking: NSAIDs, Aminoglycosides

Disqualifiers: Peripheral neuropathy, Kidney failure, Cardiac disease, Hepatitis, HIV, 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: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs to treat multiple myeloma, a type of blood cancer. The drugs include Bortezomib (Velcade), Daratumumab (Darzalex), Dexamethasone, and Lenalidomide. The goal is to determine the effectiveness of this drug combination in managing the disease in elderly patients who cannot undergo stem cell transplants. Participants will receive the treatment until the disease progresses or they experience intolerable side effects. This trial suits those newly diagnosed with multiple myeloma, experiencing symptoms like bone pain or weakness, and unable to have a stem cell transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you should avoid NSAIDs, IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2 weeks of enrollment, except aspirin. 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 the treatment using daratumumab, bortezomib, lenalidomide, and dexamethasone is generally well-tolerated by patients with multiple myeloma. The FDA has approved these drugs for treating this condition, indicating they have passed safety tests.

Early findings suggest that combining daratumumab with the other drugs may cause some side effects, but they are usually manageable. Common side effects include fatigue, nausea, and low blood counts, while serious side effects are less common.

As this trial is in an early stage, it focuses on safety and side effects. Participants receive close monitoring to quickly identify and manage any issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this quadruple drug therapy for multiple myeloma because it combines four powerful treatments: Bortezomib, Daratumumab, Dexamethasone, and Lenalidomide. Unlike standard regimens that typically use three drugs, this approach adds Daratumumab, a monoclonal antibody, which specifically targets cancer cells, potentially improving treatment efficacy. Additionally, the use of Daratumumab in a subcutaneous form may offer a more convenient and patient-friendly administration method compared to traditional intravenous infusions. By integrating this innovative combination and delivery method, the treatment aims to enhance outcomes and offer a more tolerable experience for patients battling multiple myeloma.

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

Research has shown that a combination of four drugs—daratumumab, bortezomib, lenalidomide, and dexamethasone—effectively treats multiple myeloma, a type of blood cancer. In this trial, participants will receive daratumumab with dose-attenuated VRd (bortezomib, lenalidomide, and dexamethasone). Studies have found that patients taking these drugs experienced significant improvements, with many seeing a decrease in cancer cells. The FDA has approved this drug mix for people newly diagnosed with multiple myeloma, highlighting its effectiveness. Patients generally tolerate the treatment well, with manageable side effects. This combination is especially promising for those who cannot undergo a stem cell transplant. Overall, evidence suggests it can help control symptoms of multiple myeloma. ^{1 2 3 4 6}

Who Is on the Research Team?

Larysa Sanchez

Principal Investigator

Icahn School of Medicine at Mount Sinai

Sundar Jagannath, MBBS

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for people aged 70 or older with newly diagnosed multiple myeloma who can't have a stem cell transplant. They should be able to perform daily activities (ECOG ≤ 2) and have measurable disease indicators. Men must use contraception if sexually active with women of childbearing potential. People are excluded if they have certain heart, lung, kidney diseases, infections, severe allergies to the drugs being tested, or other health conditions that could affect drug absorption or pose risks.

Inclusion Criteria

I am 70 or older, ineligible for a specific stem cell transplant, and can care for myself despite my myeloma.

You have a measurable amount of M-protein in your blood or urine, or abnormal results in a serum free light chain assay.

I have been newly diagnosed with multiple myeloma and have not received treatment.

Exclusion Criteria

You have tested positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

Your platelet count is less than 75,000 cells per cubic millimeter.

I haven't had any cancer treatment in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Initial Treatment

Participants receive 12 cycles of daratumumab in combination with dose-attenuated VRd

48 weeks

12 visits (in-person, monthly)

Maintenance Therapy

Participants receive maintenance therapy with daratumumab and either lenalidomide or ixazomib based on cytogenetic risk status

Up to 2 years

Monthly visits (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness after treatment

At least 1 year

Periodic visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests a combination of subcutaneous daratumumab with lower doses of bortezomib, lenalidomide (revlimid), and dexamethasone in elderly patients who cannot undergo transplantation. The treatment continues until disease progression or unacceptable side effects occur while monitoring for safety and effectiveness.

How Is the Trial Designed?

Group I: Daratumumab with dose-attenuated VRd Experimental Treatment 5 Interventions

SubQ Daratumumab with Dose-Attenuated VRd

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?

Larysa Sanchez

Lead Sponsor

Trials

2

Recruited

40+

Ajai Chari

Lead Sponsor

Trials

5

Recruited

100+

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

In a study comparing two induction therapies for newly diagnosed multiple myeloma, the quadruplet regimen (D-VTd) showed significantly better response rates after treatment, with 90.5% achieving complete remission (CR) or stringent complete remission (sCR) compared to 68.6% in the triplet regimen (VRd).

The quadruplet regimen (D-VTd) also resulted in a higher rate of very good partial response (VGPR or better) at 93%, compared to 67.6% in the triplet regimen (VRd), although VRd was associated with a higher incidence of skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study. Byun, JM., Park, SS., Yoon, SS., et al.[2023]

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]

In a study of 78 patients with relapsed or refractory multiple myeloma, the combination of bortezomib, bendamustine, and prednisone showed a 69% response rate, indicating significant efficacy in treating this condition.

Patients without severe prior hematological toxicities had a median progression-free survival (PFS) of 11 months and overall survival (OS) of 50 months, while those with severe toxicities had much poorer outcomes, highlighting the importance of patient health status in treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. Pönisch, W., Bourgeois, M., Moll, B., et al.[2021]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

Bortezomib is recommended for use in both newly diagnosed and relapsed/refractory multiple myeloma patients, whether they are eligible for autologous stem cell transplantation or not, based on a systematic review of evidence.

The guidelines also emphasize the importance of monitoring and managing potential toxicities associated with bortezomib treatment, such as the risk of herpes zoster reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in multiple myeloma: a practice guideline. Kouroukis, CT., Baldassarre, FG., Haynes, AE., et al.[2015]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

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]

The introduction of bortezomib and lenalidomide, especially in combination with dexamethasone, has significantly improved treatment outcomes for multiple myeloma, leading to better response rates and longer durations of response compared to older therapies.

Triplet regimens like lenalidomide, bortezomib, and dexamethasone (RVD) have shown enhanced efficacy and good tolerability in both newly diagnosed and relapsed/refractory multiple myeloma patients, indicating a promising approach for improving patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of multiple myeloma with lenalidomide and bortezomib combination therapy]. Takeda, Y., Sakaida, E., Nakaseko, C.[2018]

Thalidomide, when used as a first-line treatment combined with conventional chemotherapy, has been shown to improve survival rates in patients over 65, despite its potential toxicity to the peripheral nervous system.

Bortezomib and lenalidomide, both effective in treating myeloma relapse, can be used in combination with dexamethasone and each other, indicating a shift towards using these agents to manage myeloma as a chronic disease rather than relying solely on traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. Moreau, P.[2019]

In a study of 68 older patients (70 years and above) with bortezomib-resistant multiple myeloma, treatment with lenalidomide and low-dose dexamethasone resulted in a positive response in all patients over a median duration of 12 months.

Despite significant renal dysfunction at the start of treatment, all patients showed improvement in renal function by the end, indicating that this combination therapy is both effective and safe for older patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted Lenalidomide Combined with Low-dose Dexamethasone Rescues Older Patients with Bortezomib-resistant Multiple Myeloma. Yamasaki, S., Kohno, K., Kadowaki, M., et al.[2018]

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]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

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. 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 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

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

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/fda-daratumumab-isatuximab-newly-diagnosed-myeloma

Darzalex Faspro, Sarclisa Approvals for Multiple Myeloma Two recent approvals by the Food and Drug Administration (FDA) broaden the initial treatment options for people who have a new diagnosis of multiple myeloma.

5. darzalex.com darzalex.com/dvrd/

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.

6. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.