Daratumumab for Smoldering Multiple Myeloma

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: IMIDs, Proteasome inhibitors

Disqualifiers: COPD, Asthma, Cardiac disease, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 20 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) to determine if it can treat conditions that often lead to multiple myeloma, such as Monoclonal Gammopathy of Unknown Significance (MGUS) and Smoldering Multiple Myeloma (SMM). The researchers aim to find out if the drug can slow down or prevent the progression of these conditions. Participants who might be suitable are those diagnosed with high-risk MGUS or low-risk SMM, especially if they have specific protein and cell levels in their blood or bone marrow. 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, you cannot take other treatments that are active against smoldering multiple myeloma or multiple myeloma while participating in this trial.

Is there any evidence suggesting that Daratumumab is likely to be safe for humans?

Research has shown that daratumumab is generally safe for people. In past studies, patients who took daratumumab experienced a low rate of serious side effects. The treatment is approved in Europe as the first option for high-risk smoldering multiple myeloma, indicating it has passed safety checks for that use. Additionally, another study found that people treated with daratumumab lived longer than those who were only monitored, further supporting its safety. While the treatment is administered through IV infusions, monitoring for any side effects during the trial remains important, despite past evidence suggesting its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for smoldering multiple myeloma?

Daratumumab is unique because it targets a specific protein called CD38 on the surface of myeloma cells, which is different from traditional treatments for smoldering multiple myeloma like watchful waiting or chemotherapy. Most treatments for this condition don't directly target the cells, but daratumumab uses a monoclonal antibody approach, directly binding to the cells and helping the immune system destroy them. Researchers are excited about daratumumab because it offers a more precise and potentially more effective method of controlling the progression of the disease, potentially delaying the advancement to active multiple myeloma.

What evidence suggests that Daratumumab might be an effective treatment for Smoldering Multiple Myeloma?

Research has shown that daratumumab, which participants in this trial will receive, may effectively treat smoldering multiple myeloma (SMM). In studies, patients who received daratumumab experienced slower disease progression compared to those who were only monitored. One study found that daratumumab reduced the risk of developing active multiple myeloma or dying by 51%. Additionally, 93% of patients treated with daratumumab were still alive after five years, a higher survival rate than those who did not receive the treatment. This evidence suggests that daratumumab could help slow the progression of multiple myeloma. ^{2 3 6 7 8}

Who Is on the Research Team?

Irene Ghobrial, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with high-risk MGUS or low-risk Smoldering Multiple Myeloma who haven't had treatment for these conditions can join. They must be in decent health, have certain blood and organ function levels, not be pregnant, and able to consent. Excluded are those with recent cancers (with exceptions), severe illnesses, major surgery within the last month, or on other clinical trials.

Inclusion Criteria

My condition is either high-risk MGUS or low-risk smoldering myeloma.

I am a woman who has been postmenopausal for at least a year or am surgically sterile.

I am of childbearing age and have a recent negative pregnancy test.

Exclusion Criteria

Serious medical or psychiatric illness likely to interfere with participation in this clinical study

I have COPD with less than half the normal lung function.

You have a known active viral infection with HIV, HBV, or HCV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Daratumumab is administered by IV infusion weekly during cycles 1 and 2, every other week during cycles 3 through 6, and monthly during cycles 7 through 20

20 months

Weekly visits during cycles 1-2, bi-weekly visits during cycles 3-6, monthly visits during cycles 7-20

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The trial is testing Daratumumab as a potential treatment for Monoclonal Gammopathy of Unknown Significance (MGUS) and Smoldering Multiple Myeloma (SMM). It's a Phase II study which means they're looking at how effective this drug is and gathering more information about its safety.

How Is the Trial Designed?

Group I: Daratumumab Experimental Treatment 1 Intervention

Daratumumab will be administered by IV infusion weekly during cycles 1 and 2 Daratumumab will be administered by IV infusion every other week during cycles 3 through 6 Daratumumab will be administered by IV infusion monthly during cycles 7 through 20

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Blood Cancer Research Partnership

Collaborator

Trials

5

Recruited

230+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

Published Research Related to This Trial

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 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]

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 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]

Elotuzumab and daratumumab are two monoclonal antibodies approved for treating relapsed or refractory multiple myeloma, with both enhancing immune system activity against myeloma cells; elotuzumab is used with lenalidomide and dexamethasone for better outcomes, while daratumumab can be effective alone or with other treatments.

The main side effects of these treatments are allergic-type infusion reactions, and there are important considerations regarding their impact on laboratory tests and potential cross-reactivity with red blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future. Sherbenou, DW., Mark, TM., Forsberg, P.[2018]

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

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]

Citations

1. cancernetwork.com cancernetwork.com/view/subcutaneous-daratumumab-improves-pfs-in-smoldering-multiple-myeloma

Subcutaneous Daratumumab Improves PFS in Smoldering ... With a median follow-up of 65.2 months, the median progression-free survival (PFS) was not reached with daratumumab vs 41.5 months with ...

2. 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 ... Overall survival was also extended with DARZALEX FASPRO®, with 5-year survival rates of 93 percent versus 86.9 percent for active monitoring (HR ...

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-darzalex-faspro-use-in-smoldering-multiple-myeloma

darzalex - Use in Smoldering Multiple Myeloma DARZALEX FASPRO significantly reduced the risk of progression to multiple myeloma (MM) or death by 51% vs active monitoring (hazard ratio [HR], 0.49; 95% ...

4. onclive.com onclive.com/view/daratumumab-significantly-improves-pfs-extends-os-in-smoldering-myeloma

Daratumumab Significantly Improves PFS, Extends OS in ... Subcutaneous daratumumab significantly improved PFS and OS in high-risk patients with smoldering multiple myeloma, reducing progression or death ...

5. myeloma.org myeloma.org/blog/fda-odac-supports-darzalex-faspro-for-hr-smm

FDA ODAC Supports Use of Darzalex Faspro for HR-SMM It's the first CD38-targeting drug approved for multiple myeloma and has been used by more than 618,000 people worldwide.

6. myeloma.org myeloma.org/fda-odac-votes-support-darzalex-faspro-high-risk-smoldering-myeloma

FDA ODAC Votes in Support of DARZALEX FASPRO for ... The US Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) voted 6-2 in favor of the benefit-risk profile of DARZALEX FASPRO.

7. jnj.com jnj.com/media-center/press-releases/european-commission-approves-darzalex-daratumumab-as-the-first-licensed-treatment-for-patients-with-high-risk-smouldering-multiple-myeloma

European Commission approves DARZALEX® ... European Commission approves DARZALEX® (daratumumab) as the first licensed treatment for patients with high-risk smouldering multiple myeloma.

8. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... Darzalex Faspro is indicated for the treatment of adult patients with multiple myeloma: in combination with bortezomib, lenalidomide, and dexamethasone for ...