Subcutaneous Daratumumab for High-Risk Smoldering Multiple Myeloma

Not currently recruiting at 254 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, Monoclonal antibodies

Disqualifiers: Multiple myeloma, Amyloidosis, 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: 6

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether daratumumab, administered by a small injection under the skin, can delay the progression of high-risk smoldering multiple myeloma, a condition that can lead to a type of blood cancer. Participants will either receive this treatment or undergo close monitoring without treatment to determine which approach is more effective. Individuals diagnosed with high-risk smoldering multiple myeloma within the last five years and who exhibit certain measurable disease signs might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, ongoing treatment with certain medications like corticosteroids above a specific dose, monoclonal antibodies, and immunomodulators is not allowed. It's best to discuss your current medications with the trial team.

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

Research has shown that daratumumab, when administered as a subcutaneous injection, is generally safe for individuals with smoldering multiple myeloma. Studies indicate it mostly causes mild side effects, consistent with known effects of the drug.

In earlier studies, serious side effects were rare. Daratumumab has been safely used in other conditions, supporting its safety profile. Previously, it was administered intravenously for multiple myeloma.

The injection form maintains a low rate of severe side effects. Overall, evidence suggests it is well-tolerated, meaning most individuals do not experience adverse reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about daratumumab SC for high-risk smoldering multiple myeloma because it offers a new method of delivery that could make treatment more accessible. Unlike traditional treatments like proteasome inhibitors or immunomodulatory drugs, daratumumab SC is administered as a subcutaneous injection, which is less invasive than intravenous options. This means patients might spend less time in the clinic and experience greater convenience. Additionally, daratumumab is a monoclonal antibody that specifically targets CD38, a protein often found on myeloma cells, potentially improving its effectiveness in halting disease progression.

What evidence suggests that daratumumab SC might be an effective treatment for high-risk smoldering multiple myeloma?

In this trial, participants will either receive daratumumab, administered as an injection under the skin, or undergo active monitoring. Research has shown that daratumumab may be promising for treating high-risk smoldering multiple myeloma (SMM). In one study, patients receiving daratumumab had not yet reached the average time before their disease worsened, while those under active monitoring had an average of 41.5 months before progression. This suggests that daratumumab might help delay disease progression. Additionally, after five years, 93% of patients on daratumumab were still alive, compared to 86.9% of those only monitored. These findings suggest that daratumumab could be an effective option for managing high-risk SMM. ^{1 4 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for people diagnosed with high-risk smoldering multiple myeloma (SMM) within the last 5 years, who have measurable disease and meet specific criteria like certain protein levels in blood/urine. They should be relatively healthy otherwise, able to perform daily activities with little or no assistance (ECOG score of 0 or 1), and women must use effective contraception. People can't join if they've had previous treatments for SMM/MM, certain bone lesions, severe kidney issues, recent other cancers except minor skin cancers or localized prostate cancer.

Inclusion Criteria

If you are a woman who could become pregnant, you need to have a negative pregnancy test within 14 days before starting the study.

I have been diagnosed with a high-risk type of early-stage multiple myeloma within the last 5 years.

I am fully active or can carry out light work.

Exclusion Criteria

You have more than one small spot in your body that is bigger than 5 millimeters when checked with MRI.

My kidney function is low, not due to multiple myeloma.

I have previously received treatments for SMM or MM, but I am on stable doses of medication for bone health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1800 mg of daratumumab subcutaneously every 28 days for up to 39 cycles or 36 months

36 months

Monthly visits for each cycle

Active Monitoring

Participants undergo regular disease evaluations without receiving study medication

36 months

Monthly evaluations

Follow-up

Participants are monitored for progression-free survival and other outcomes post-treatment

Up to 8 years

Every 6 months post-progression

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab SC

Trial Overview The study tests whether daratumumab given under the skin prolongs the time patients live without their disease getting worse compared to just watching and waiting. Daratumumab is an antibody that targets cancer cells. Participants will either receive this drug subcutaneously along with rHuPH20 (an enzyme to help absorption) or undergo active monitoring without treatment.

How Is the Trial Designed?

Group I: Arm B: Daratumumab SC Experimental Treatment 1 Intervention

Participants will receive 1800 milligram (mg) of daratumumab co-formulated with 2000 units per milliliter (U/mL) of recombinant human hyaluronidase (rHuPH20) by subcutaneous (SC) injection until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion.

Group II: Arm A: Active Monitoring Active Control 1 Intervention

Participants randomized to active monitoring will receive no study medication, but will undergo the same disease evaluations at the same frequency as participants randomized to daratumumab.

Daratumumab SC 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

Approved in United States as Darzalex for:

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

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

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]

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, now available in a subcutaneous form, significantly reduces administration time from 7 hours to just 3-5 minutes compared to the intravenous version, making it more convenient for patients.

The subcutaneous formulation also has lower rates of infusion-related reactions (less than 10% compared to 50% for intravenous), while maintaining similar efficacy and safety profiles, which enhances its overall usability in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. Sanchez, L., Richter, J., Cho, HJ., et al.[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]

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, 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]

Citations

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

FDA ODAC Supports Use of Darzalex Faspro for HR-SMM The study showed clear and meaningful improvements in progression-free survival (PFS).

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2409029

Daratumumab or Active Monitoring for High-Risk ... The phase 2 CENTAURUS study showed that daratumumab had single-agent activity in patients with intermediate-risk or high-risk smoldering multiple myeloma.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39652675/

Daratumumab or Active Monitoring for High-Risk ... Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was ...

4. 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 ...

5. 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 ...

6. 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% ...

7. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/darzalex

Darzalex | European Medicines Agency (EMA) Darzalex was shown to prolong the time patients with smouldering multiple myeloma at high risk of progressing to multiple myeloma live without their disease ...