Daratumumab-Based Therapy for Multiple Myeloma

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Antibiotics, Anticancer agents

Disqualifiers: Severe infection, Prior malignancy, COPD, 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 tests a combination of medications to evaluate their effectiveness for older adults with multiple myeloma, a type of blood cancer. The study focuses on treatments that include daratumumab, a drug known to target cancer cells, along with supportive medications like dexamethasone, bortezomib (also known as Velcade), and lenalidomide. Participants will receive different combinations of these drugs to identify the most effective approach. Individuals with active multiple myeloma who experience symptoms such as high calcium levels or bone issues and have not yet undergone chemotherapy might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use other anti-cancer treatments during the study, except for hormonal therapy, which is allowed.

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

Research shows that treatments using daratumumab are generally well-tolerated by people with multiple myeloma. The FDA has approved the combination of daratumumab with bortezomib and dexamethasone for treating this condition, indicating a review of its safety by health authorities.

Other studies have found that adding lenalidomide to daratumumab and dexamethasone is also effective and generally well-tolerated. Reported side effects are similar to those expected from multiple myeloma treatments, such as mild to moderate tiredness or nausea.

Since this study is in phase 2, earlier research has already assessed the treatment's safety. This suggests it is likely safe enough for testing in more people. However, like any treatment, some risks may still exist, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the daratumumab-based therapy for multiple myeloma because it offers a fresh approach to tackling this cancer. Unlike standard treatments, which often involve chemotherapy or stem cell transplants, daratumumab specifically targets CD38, a protein found on the surface of myeloma cells. This targeted action can potentially improve treatment effectiveness while minimizing side effects. Additionally, the therapy's use of subcutaneous injections makes it more convenient compared to traditional intravenous methods. The combination of daratumumab with other drugs like bortezomib or lenalidomide could further enhance its cancer-fighting power, offering hope for better patient outcomes.

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

Research has shown that treatments using daratumumab are promising for multiple myeloma, especially when combined with other drugs. In this trial, one group of participants will receive daratumumab with dexamethasone and lenalidomide, a combination that has greatly improved the time patients live without their cancer worsening, with about 91% of patients responding well. Another group will explore adding bortezomib to daratumumab and dexamethasone, which has significantly improved survival rates. These combinations help people with multiple myeloma live longer without their cancer worsening. Overall, using daratumumab with these other drugs shows strong results in extending life and delaying disease progression. ^{5 6 7 8 9}

Who Is on the Research Team?

Rachid C Baz, MD

Principal Investigator

H. Lee Moffitt Cancer & Research Institute

Are You a Good Fit for This Trial?

This trial is for older adults (65+) with newly diagnosed multiple myeloma who haven't had chemotherapy but may have had palliative radiotherapy or a small dose of dexamethasone. They must be able to follow the study schedule, use contraception if necessary, and have adequate organ function and bone marrow capacity. People with severe other illnesses, active infections requiring IV antibiotics, certain viral infections (HIV, hepatitis B/C), or uncontrolled medical conditions are excluded.

Inclusion Criteria

You have high levels of a protein called paraprotein in your blood or urine.

I am over 65 and have health issues that may worsen with intense chemotherapy.

My kidneys are functioning well enough, as per a specific test.

Exclusion Criteria

You have tested positive for hepatitis C.

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

My only sign of plasma cell disorder is a single bone or soft tissue tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and dexamethasone for 2 months. Based on response, lenalidomide or bortezomib may be added.

8 weeks

Weekly visits for subcutaneous injections and oral medication

Response Evaluation

Participants are evaluated for response to determine continuation or modification of treatment

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview

The study tests daratumumab-based therapies combined with oral dexamethasone, lenalidomide pills, and bortezomib injections in treating multiple myeloma in older adults. It's designed to see how well patients respond to this combination therapy without undergoing high-dose chemotherapy with stem-cell transplantation due to their age or coexisting conditions.

How Is the Trial Designed?

Group I: C: Daratumumab, Dexamethasone and Bortezomib Experimental Treatment 3 Interventions

Participants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m\^2 Days 1,8 and 15 of each 28 day treatment cycle.

Group II: B: Daratumumab, Dexamethasone and Lenalidomide Experimental Treatment 3 Interventions

Participants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.

Group III: A: Daratumumab & Dexamethasone Experimental Treatment 2 Interventions

All participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

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

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]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

In a study of 737 patients with newly diagnosed multiple myeloma, the addition of daratumumab to lenalidomide and dexamethasone significantly reduced the risk of disease progression or death, with a hazard ratio of 0.56, indicating a 44% lower risk compared to the control group.

Patients receiving daratumumab had a higher rate of complete response (47.6% vs. 24.9%) and a greater percentage achieving minimal residual disease status (24.2% vs. 7.3%), although they also experienced more severe side effects like neutropenia and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Facon, T., Kumar, S., Plesner, T., et al.[2023]

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]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Daratumumab, a human CD38 monoclonal antibody, shows significant effectiveness in killing multiple myeloma cells that are resistant to lenalidomide and bortezomib, as demonstrated in both ex vivo assays and in vivo mouse models.

The combination of daratumumab with lenalidomide enhances the lysis of resistant myeloma cells and effectively reduces tumor growth in a xenograft model, suggesting a promising new treatment option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib. Nijhof, IS., Groen, RW., Noort, WA., et al.[2020]

In a study of 162 multiple myeloma patients who received daratumumab, combining it with lenalidomide (DRd) showed no significant difference in progression-free survival (PFS) compared to combining it with pomalidomide (DPd) for those previously treated with lenalidomide.

Both treatment combinations (DRd and DPd) were found to be effective options for patients with relapsed/refractory multiple myeloma, indicating that daratumumab with lenalidomide remains a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. Alhaj Moustafa, M., Parrondo, R., Abdulazeez, MF., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10022849/

Overall Survival With Daratumumab, Lenalidomide, and ...

Daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone ( ...

2.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2024/multiple-myeloma-darzalex-plus-vrd

Daratumumab Plus Standard Therapy for Multiple Myeloma

Early results from the trial suggest that daratumumab may be most effective when added to all three phases of the standard treatment regimen.

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onclive.com

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Iberdomide/Daratumumab/Dexamethasone Is Effective in ...

The iberdomide-daratumumab-dexamethasone regimen achieved a 93.1% overall response rate in frail, transplant-ineligible multiple myeloma ...

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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

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darzalex.com

darzalex.com/clinical-results/

Clinical Results

91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).

6.

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.

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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.

8.

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TECVAYLI® plus DARZALEX FASPRO® combination ...

The study evaluates the efficacy and safety of TECVAYLI® (teclistamab-cqyv) in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase- ...

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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.