Daratumumab for Multiple Myeloma

Recruiting at 95 trial locations

Overseen By Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Daratumumab

Disqualifiers: Allergies, Investigational vaccines, 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: 3 years 7 months

500 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to provide ongoing access to study treatments for participants with multiple myeloma or smoldering multiple myeloma benefiting from treatment in certain Janssen Research and Development (R\&D) studies that use daratumumab as part of the study treatment regimen: access for all participants regardless of treatment group in daratumumab studies and access to participants in daratumumab-containing arms in the non-daratumumab studies will be allowed from studies which have reached clinical cutoff for final analysis. Certain long-term safety data will continue to be collected from study participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have taken any disallowed therapies between the completion of the parent study and the start of this study.

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-of-its-kind monoclonal antibody that targets a specific protein (CD38) on multiple myeloma cells, leading to their destruction. 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 treatments. ^{1 2 3 4 6}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for individuals with multiple myeloma or smoldering multiple myeloma who are benefiting from ongoing Janssen R&D studies involving daratumumab. Participants must not be pregnant, agree to contraception, have signed an informed consent form, and adhere to lifestyle restrictions. They should continue to benefit from the treatment without disease progression or unmanageable toxicity.

Inclusion Criteria

Willing and able to adhere to the lifestyle restrictions specified in this protocol

I am a woman who can have children, have tested negative for pregnancy, and agree to ongoing pregnancy tests.

I agree not to donate sperm during and for 3 months after the study.

Exclusion Criteria

I have not taken any treatments not allowed by this study since my last study ended.

I haven't had any experimental or live vaccines in the last 4 weeks, except for COVID-19.

Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab as monotherapy or in combination with standards of care treatment

3 years 7 months

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years 7 months

Open-label extension

Participants continue to receive daratumumab treatment long-term

Long-term

Treatment Details

Interventions

• Daratumumab

Trial Overview The study provides access to treatments like Daratumumab (alone or with other drugs) for participants in previous trials where it showed benefits. It aims to allow continued use of these treatments and collect long-term safety data on their effectiveness against multiple myeloma.

Participant Groups

Group I: Daratumumab Experimental Treatment 5 Interventions

Participants will receive a single dose of daratumumab 16 milligrams per kilograms (mg/kg) intravenous (IV) or 1800 mg subcutaneous (SC) infusion on Cycle 1 Day 1 (28-day cycle), as monotherapy or in combination with standards of care treatment (that is, pomalidomide and dexamethasone, lenalidomide and dexamethasone, carfilzomib and dexamethasone) or standards of care treatment alone, depending on the treatment received in the parent study. Participants who received daratumumab IV during the parent study, will have an option to switch to daratumumab SC on Day 1 of any cycle during this long-term extension study.

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?

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

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 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 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]

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 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, 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: First Global Approval. [2018]

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

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