Daratumumab for Multiple Myeloma

Recruiting at 28 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

570 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether taking daratumumab (a cancer drug) for a shorter period is as effective as continuous use in treating multiple myeloma, a type of blood cancer. Participants will either continue with the standard treatment of daratumumab, lenalidomide, and dexamethasone or stop daratumumab after about a year and a half while continuing the other two drugs. It is ideal for individuals with multiple myeloma who cannot undergo a transplant and have experienced some success with the standard treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that daratumumab is generally well-tolerated by patients with multiple myeloma. In one study, the most common side effect of using daratumumab alone was an upper respiratory tract infection, affecting 20% or more of patients. This indicates that some people might experience cold-like symptoms, but serious side effects occur less frequently.

Daratumumab has been used for some time to treat multiple myeloma and has shown promising results. For instance, in one study, patients on a daratumumab-based treatment had a 95% chance of not experiencing disease progression over four years. This suggests the treatment is both effective and safe for long-term use.

Overall, daratumumab has a strong safety record, as the FDA has already approved it for treating multiple myeloma. This approval indicates that the treatment has undergone thorough safety testing in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about daratumumab for multiple myeloma because it targets the CD38 protein on myeloma cells, marking them for destruction by the immune system. This is different from traditional treatments like lenalidomide and dexamethasone, which focus on modulating the immune response and reducing inflammation. Daratumumab's ability to directly attack cancer cells offers a promising new approach, potentially leading to better outcomes for patients. Additionally, when combined with standard therapies, it may enhance their effectiveness, providing a comprehensive attack on the disease.

What evidence suggests that stopping daratumumab after a year and a half might be as effective for multiple myeloma as continuous treatment?

Studies have shown that daratumumab effectively treats multiple myeloma. In this trial, one group of participants will receive a treatment plan that includes daratumumab, lenalidomide, and dexamethasone. Research indicates that patients using a treatment plan with daratumumab have a 95% chance of maintaining "progression-free survival" over four years, meaning the disease does not worsen during this time. Additionally, daratumumab has lowered the risk of the disease becoming active by 51% in patients with a specific type of multiple myeloma. These results suggest that daratumumab is a strong option for managing multiple myeloma. ^{1 2 3 4 6}

Who Is on the Research Team?

Hira Mian

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Lenalidomide & Dexamethasone Experimental Treatment 2 Interventions

Group II: Daratumumab, Lenalidomide, Dexamethasone & Isatuximab Active Control 4 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+

Published Research Related to This Trial

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]

Citations

1.

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 ...

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen shows 95 percent progression-free survival at four years in transplant- ...

2.

darzalex.com

darzalex.com/clinical-results/

Clinical Results

A study confirmed that DARZALEX FASPRO ® gave patients results comparable to the IV formulation of DARZALEX ® in treating multiple myeloma when used by itself.

3.

cancer.gov

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

Daratumumab Plus Standard Therapy for Multiple Myeloma

Slightly more patients in the daratumumab group than the standard treatment group were able to receive a stem cell transplant (90% versus 87%).

4.

jnj.com

jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-shows-51-percent-reduction-in-risk-of-progression-to-active-multiple-myeloma-for-patients-with-high-risk-smoldering-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase ...

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) shows 51 percent reduction in risk of progression to active multiple myeloma for patients ...

5.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT05511428

Home Based Daratumumab Administration for Patients ...

This clinical trial tests the treatment effect of home based daratumumab administration in treating patients with multiple myeloma. Darzalex Faspro is a ...

6.

darzalexhcp.com

darzalexhcp.com/frontline-dvrd/

Frontline DVRd

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse ...