Daratumumab-based Therapy for Multiple Myeloma

Not currently recruiting at 3 trial locations

Overseen By Matthew Pianko, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Renal insufficiency, Hepatic impairment, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for people with multiple myeloma, a type of blood cancer. The study tests a combination of medications, including daratumumab (an immunotherapy drug), to determine if they can help more patients achieve minimal residual disease (MRD)-negative status, meaning no detectable signs of cancer. The trial includes an initial phase of treatment and, if needed, additional treatment to consolidate the results. This trial suits individuals diagnosed with active multiple myeloma who can handle the treatment regimen and have not yet undergone more than one round of anti-myeloma therapy. As a Phase 2 trial, the research focuses on measuring 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, if you are using strong CYP3A4 inducers, you may need to switch to an alternative medication while receiving Bortezomib.

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

Research has shown that treatments using daratumumab have been tested in people with multiple myeloma and have demonstrated promising safety results. When combined with other drugs like lenalidomide and dexamethasone, daratumumab is usually well-tolerated. In past studies, most patients managed side effects such as tiredness and nausea without major issues.

Lenalidomide and dexamethasone are also commonly used in treating multiple myeloma and have well-known safety records. Typical side effects include low blood counts and a higher risk of infections, but these can usually be managed with medical help.

The FDA has approved daratumumab for treating multiple myeloma, supporting its safety. While all treatments can have side effects, evidence so far suggests these therapies are generally safe for most patients. ^{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 unique approach compared to existing treatments. Most treatments for multiple myeloma, like bortezomib or lenalidomide alone, focus on suppressing the cancer cells' growth. However, Daratumumab is an antibody that specifically targets CD38, a protein found on the surface of multiple myeloma cells, marking them for destruction by the immune system. This targeted mechanism is combined with a phased regimen that adapts based on the patient's response, potentially enhancing the treatment's effectiveness and personalizing the approach to each patient's needs.

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

Research has shown that the combination of daratumumab, lenalidomide, and dexamethasone (Dara-Rd), administered during the induction phase of this trial, effectively treats multiple myeloma, a type of blood cancer. Studies have found that this combination can reduce cancer cells to very low levels, achieving minimal residual disease (MRD) negativity. Participants with MRD positivity after induction will receive an additional drug, bortezomib, during the consolidation phase (Dara-RVd), which has further reduced cancer cells in past studies. The FDA has approved this combination for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplants. Patients using these treatments have experienced longer periods without cancer progression. Overall, evidence supports the effectiveness of these combinations in managing multiple myeloma. ^{4 5 6 7 8}

Who Is on the Research Team?

Jing Ye, M.D.

Principal Investigator

MD Anderson

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed Multiple Myeloma who have measurable disease and can tolerate treatments, including high-dose chemotherapy and stem cell transplant if needed. Participants must not have had more than one cycle of myeloma therapy before joining, be free from certain blood/liver diseases, HIV, Hepatitis B/C, other active cancers in the last five years, or significant heart or lung conditions.

Inclusion Criteria

I have a bone marrow or tissue sample available for testing.

I am registered and comply with the REMS program for lenalidomide.

I am a man willing to follow specific rules about contraception or abstinence.

Exclusion Criteria

I am allergic or cannot take certain medications required for this study.

I am not pregnant or breastfeeding.

Participation in other clinical trials within 30 days of the start of this trial and throughout the duration of this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with Daratumumab, Lenalidomide, and Dexamethasone (Dara-Rd)

24 weeks

Regular visits as per protocol

Consolidation Therapy

Participants with MRD-positive status receive consolidation therapy with Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (Dara-RVd)

12 weeks

Regular visits as per protocol

Maintenance Therapy

Participants receive maintenance therapy with Daratumumab and Lenalidomide (Dara-R), followed by Lenalidomide alone until progression or intolerance

51 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 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 + lenalidomide + dexamethasone) as initial treatment. If minimal residual disease is detected afterward, an additional drug (bortezomib) is added. The approach adapts to each patient's response to maximize chances of eliminating all signs of cancer at a microscopic level.

How Is the Trial Designed?

Group I: Dara-Rd followed by Dara-RVd Experimental Treatment 4 Interventions

* Induction regimen with Daratumumab, Lenalidomide and Dexamethasone (Dara-Rd) in all study subjects, weeks 1-24 * Consolidation regimen with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (Dara-RVd) in post-induction MRD+ population, weeks 25-36 * Maintenance regimen with Daratumumab and Lenalidomide (Dara-R) in all study subjects, weeks 37-88 * Maintenance regimen with lenalidomide (R) until progression or intolerance

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

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 is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

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]

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]

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]

Daratumumab combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

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 received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

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