Daratumumab for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Daratumumab

Disqualifiers: Prior ASCT, Amyloidosis, Active infection, 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: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well daratumumab works in treating transplant-eligible patients with multiple myeloma. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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 lead to significant responses in patients with multiple myeloma, including those who have not responded to other treatments. It has been shown to improve progression-free survival and induce deep and lasting responses in various clinical trials. ^{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 the CD38 protein on multiple myeloma cells, leading to their destruction through various immune mechanisms. 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 therapies. ^{1 2 3 4 6}

Research Team

Sikander Ailawadhi

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for transplant-eligible patients with multiple myeloma who have had prior therapy but not daratumumab. They must show measurable cancer markers, be in decent physical condition (ECOG 0-2), and have adequate organ function. Pregnant or breastfeeding women, those unwilling to use contraception, or individuals with certain medical conditions like severe infections, heart issues, or other cancers are excluded.

Inclusion Criteria

My multiple myeloma is measurable by specific medical criteria.

I can take care of myself and am up and about more than half of my waking hours.

My white blood cell count is healthy without needing medication.

Exclusion Criteria

I have previously been treated with daratumumab.

I have not needed IV antibiotics for an infection in the last 14 days.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation I

Patients receive daratumumab intravenously on days 1, 8, 15, and 22 of cycles 1-2, and on days 1 and 15 of cycles 3-4. Treatment repeats every 28 days for up to 4 cycles.

16 weeks

Consolidation II

Patients undergo autologous stem cell transplant (ASCT) beginning 8 weeks after completion of daratumumab cycle 2 or 4.

8 weeks

Maintenance

Patients receive daratumumab IV on day 1 and lenalidomide orally daily on days 1-21. Treatment repeats every 28 days for up to 12 cycles.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

Treatment Details

Interventions

• Daratumumab

Trial Overview The study is testing the effectiveness of daratumumab in treating multiple myeloma in patients eligible for a stem cell transplant. Daratumumab is an antibody that targets cancer cells to prevent their growth. The trial includes autologous hematopoietic stem cell transplantation and lenalidomide as part of the treatment process.

Participant Groups

Group I: Treatment (daratumumab, ASCT, lenalidomide) Experimental Treatment 3 Interventions

CONSOLIDATION I: Patients receive daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, and on days 1 and 15 of cycles 3-4. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION II: Beginning 8 weeks after completion of daratumumab cycle 2 or 4, patients undergo ASCT. MAINTENANCE: Within 14 days after completion of day 100 visit post-SCT, patients receive daratumumab IV on day 1 and lenalidomide PO daily on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients who are still maintaining response continue to receive daratumumab IV every 3 months in the absence of disease progression or unacceptable toxicity.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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

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

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

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

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

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

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]