Subcutaneous Daratumumab for High-Risk Smoldering Multiple Myeloma

Recruiting at 209 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

390 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).

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.

What data supports the effectiveness of the drug Daratumumab SC for high-risk smoldering multiple myeloma?

Daratumumab, a drug targeting a protein on multiple myeloma cells, has shown effectiveness in treating multiple myeloma by increasing patient response rates and prolonging the time before the disease worsens. The subcutaneous form of this drug is also associated with fewer side effects compared to the intravenous form, making it a promising option for patients. ^{1 2 3 4 5}

Is subcutaneous daratumumab safe for humans?

Subcutaneous daratumumab (also known as Darzalex Faspro) has been shown to have a similar safety profile to its intravenous form, with fewer infusion-related reactions and a shorter administration time. The most common serious side effects are related to blood cell counts, such as low levels of white blood cells, but overall, it is considered to have an acceptable safety profile for treating multiple myeloma. ^{1 2 3 6 7}

What makes the drug Daratumumab SC unique for treating high-risk smoldering multiple myeloma?

Daratumumab SC is unique because it is administered subcutaneously (under the skin) rather than intravenously, which significantly reduces the time needed for administration and lowers the risk of infusion-related reactions compared to the traditional intravenous method. ^{2 5 6 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

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 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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

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, 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, 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, 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, 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]

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

Daratumumab: First Global Approval. [2018]

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

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

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

'Fast but not so Furious': Short observation time after subcutaneous Daratumumab administration is both a safe and cost-effective strategy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. [2021]

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

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]

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

Transition from Intravenous to Subcutaneous Daratumumab Formulation in Clinical Practice. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. [2020]