Daratumumab for Smoldering Multiple Myeloma

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

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug as a possible treatment for Monoclonal Gammopathy of Unknown Significance (MGUS) or Smoldering Multiple Myeloma (SMM). The drug involved in this study is: -Daratumumab

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.

What data supports the effectiveness of the drug Daratumumab for treating smoldering multiple myeloma?

Daratumumab has shown effectiveness in treating multiple myeloma, a type of blood cancer, by helping the immune system attack cancer cells. In studies, it has been effective as a single treatment and in combination with other drugs, showing rapid and lasting responses in patients with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

Is daratumumab safe for humans?

Daratumumab, also known as Darzalex, has been studied for safety in patients with multiple myeloma. Common side effects include low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), low red blood cell counts (anemia), pneumonia, and infusion-related reactions. Overall, it has an acceptable safety profile, especially when used in combination with other treatments. ^{1 3 6 7 8}

What makes the drug Daratumumab unique for treating smoldering multiple myeloma?

Daratumumab is unique because it is a monoclonal antibody that specifically targets the CD38 protein on myeloma cells, leading to their destruction through various immune system mechanisms. It is also notable for its use in patients who have not responded to other treatments, offering a new option for those with limited alternatives. ^{1 2 3 4 6}

Research Team

Irene Ghobrial, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

I am 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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 Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

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+

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, 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]

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 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, 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]

References

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

Daratumumab: First Global Approval. [2018]

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

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

3. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

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

Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma. [2018]

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

Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future. [2018]

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

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

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

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