Daratumumab-based Therapy for Multiple Myeloma

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

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

57 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 2 trial will test whether the combination of DaraRd (daratumumab + lenalidomide + dexamethasone) as induction therapy, followed by DRVd (daratumumab + lenalidomide + bortezomib + dexamethasone) consolidation therapy, if needed, will result in more patients achieving minimal residual disease (MRD)-negative status, relative to the standard of care. Consolidation therapy will be administered only to those patients with MRD-positive status after induction therapy. This is a study based on adaptive design for decision making of treatment options. Duration of therapy (daratumumab cycles) will depend on individual approach, response, evidence of disease progression and tolerance.

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.

What data supports the effectiveness of the drug Daratumumab-based Therapy for Multiple Myeloma?

Research shows that Daratumumab, when combined with other drugs like bortezomib and lenalidomide, significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with multiple myeloma. The combination therapy has shown an overall response rate of 80% in heavily treated patients, indicating it is effective in managing the disease. ^{1 2 3 4 5}

Is daratumumab-based therapy safe for humans?

Daratumumab-based therapy, often combined with drugs like lenalidomide, bortezomib, and dexamethasone, has been generally well-tolerated in clinical trials for multiple myeloma. Common side effects include low blood cell counts (neutropenia, thrombocytopenia, anemia), infections, and infusion-related reactions, but these are consistent with the known safety profiles of the drugs involved. ^{2 3 6 7 8}

What makes the drug Daratumumab-based therapy unique for treating multiple myeloma?

Daratumumab-based therapy is unique because it includes Daratumumab, a monoclonal antibody that targets CD38 on multiple myeloma cells, enhancing the immune system's ability to kill these cancer cells. This drug combination has shown to significantly prolong progression-free survival and induce deep and durable responses in patients, offering a novel approach compared to traditional treatments. ^{1 2 3 4 5}

Research Team

Jing Ye, M.D.

Principal Investigator

MD Anderson

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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, 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, 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 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 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

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. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. [2018]

5. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

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

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]

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

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

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

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]