Daratumumab for Multiple Myeloma

Recruiting at 22 trial locations

Overseen By Annette Hay

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must be taking: Daratumumab, Lenalidomide, Dexamethasone

Must not be taking: Other anti-cancer therapy

Disqualifiers: Amyloidosis, POEMS syndrome, Waldenstrom's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Indefinite, as long as benefiting

559 Participants Needed

Trial Summary

What is the purpose of this trial?

Currently, daratumumab, lenalidomide, and dexamethasone are given continuously (non-stop). Some recent observations suggest that stopping daratumumab after about a year and a half of treatment may work just as well as giving it continuously with lenalidomide and dexamethasone. This study is being done to answer the question: is less daratumumab treatment as good as more?

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 be on other anti-cancer treatments that would interfere with the trial's protocol.

What data supports the effectiveness of the drug Daratumumab for treating multiple myeloma?

Research shows that Daratumumab, when used alone or in combination with other drugs, can significantly improve response rates and prolong the time patients live without their disease getting worse. It has been effective in patients who have tried other treatments without success, making it a valuable option for those with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

How is the drug Daratumumab unique in treating multiple myeloma?

Daratumumab is unique because it is a first-in-class monoclonal antibody that targets the CD38 protein on multiple myeloma cells, leading to their destruction through various immune mechanisms. It can be administered intravenously or subcutaneously, and it has shown effectiveness both as a standalone treatment and in combination with other drugs, offering a new option for patients who have not responded to other therapies. ^{1 2 4 5 6}

Research Team

Hira Mian

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario Canada

Eligibility Criteria

This trial is for older adults who can't have a bone marrow transplant and are newly diagnosed with multiple myeloma. They should have measurable disease, been treated with daratumumab-lenalidomide-dexamethasone for 18-20 cycles, and shown some response to treatment. Participants must be able to complete questionnaires in certain languages, follow the study's procedures, use effective birth control if needed, and start the treatment within two days of joining.

Inclusion Criteria

Protocol treatment to begin within 2 working days of participant enrollment

Measurable disease at the time of diagnosis, as defined by specific criteria

Obtained at least a partial response per the standard 2016 IMWG criteria

Exclusion Criteria

Known history of specific conditions

Known human immunodeficiency virus (HIV) with CD4 count < 350 cells/microliter, with specific requirements for HIV-positive patients

Patients receiving concurrent treatment that would impact protocol compliance

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, lenalidomide, and dexamethasone continuously or stop daratumumab after about a year and a half

Indefinite, as long as benefiting

Follow-up

Participants are monitored for safety and effectiveness after treatment

8.1 years

Treatment Details

Interventions

• Daratumumab

Trial Overview The study tests whether giving daratumumab for a fixed period (about 1.5 years) combined with lenalidomide and dexamethasone is as effective as continuing it non-stop in treating multiple myeloma in patients who aren't eligible for a bone marrow transplant.

Participant Groups

Group I: Lenalidomide & Dexamethasone Experimental Treatment 2 Interventions

Group II: Daratumumab, Lenalidomide & Dexamethasone Active Control 3 Interventions

Standard of Care

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Myeloma Canada

Collaborator

Trials

2

Recruited

640+

Findings from Research

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 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]

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]

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 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]

References

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

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

2. Spain pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Daratumumab: First Global Approval. [2018]

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

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