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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of daratumumab, a therapy targeting cancer cells, for individuals with multiple myeloma, a type of blood cancer. Participants will receive daratumumab alongside other treatments to determine if it helps prevent cancer growth or spread. The trial targets those eligible for a stem cell transplant who are already managing multiple myeloma. It may suit individuals who have multiple myeloma, qualify for a transplant, and have not previously received this specific treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that daratumumab is a promising treatment for multiple myeloma, a type of blood cancer. Studies indicate it works as well as other treatments when used alone, and patients generally tolerate it well. However, infections, especially upper respiratory infections like colds, commonly occur as a side effect. These side effects can usually be managed. Daratumumab remains under study, and the safety information so far appears positive. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which often involve various combinations of drugs, daratumumab is a monoclonal antibody that specifically targets a protein called CD38 on the surface of myeloma cells. This targeted approach allows it to precisely attack cancer cells while sparing most healthy cells. Researchers are excited about daratumumab because its unique mechanism of action not only enhances the immune system's ability to fight the cancer but also offers a promising option for patients who may not respond well to conventional therapies. Additionally, when combined with an autologous stem cell transplant (ASCT) and lenalidomide, daratumumab has the potential to improve long-term outcomes and maintain remission with fewer side effects than traditional chemotherapy.

What evidence suggests that daratumumab might be an effective treatment for multiple myeloma?

Research has shown that daratumumab is highly effective for treating multiple myeloma, a type of blood cancer. One study found that patients eligible for a transplant and treated with a regimen including daratumumab had a 95% chance of the cancer not worsening over four years. Another study reported that 91.7% of patients responded well to treatment with daratumumab. In this trial, participants will receive daratumumab in combination with ASCT and lenalidomide. Previous studies suggest that combining daratumumab with other treatments results in a positive response in all newly diagnosed patients. These findings indicate that daratumumab effectively stops the spread of cancer cells in multiple myeloma. ^{1 2 6 7 8}

Who Is on the Research Team?

Sikander Ailawadhi

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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.

Pregnant women

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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]

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]

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. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen shows 95 percent progression-free survival at four years in transplant- ...

2. darzalex.com darzalex.com/clinical-results/

Clinical Results A study confirmed that DARZALEX FASPRO ® gave patients results comparable to the IV formulation of DARZALEX ® in treating multiple myeloma when used by itself.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141371/

Real-world data on the use of subcutaneous daratumumab ... As of the data cutoff (August 8, 2023), 49 patients were included. By the end of consolidation, 91.7% of patients achieved an overall response ( ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/multiple-myeloma-darzalex-plus-vrd

Daratumumab Plus Standard Therapy for Multiple Myeloma Slightly more patients in the daratumumab group than the standard treatment group were able to receive a stem cell transplant (90% versus 87%).

5. jnj.com jnj.com/media-center/press-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care

TECVAYLI® plus DARZALEX FASPRO® combination ... In transplant-eligible patients with newly diagnosed multiple myeloma, a 100 percent overall response rate was achieved when given as the first ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-darzalex-faspro-adverse-event-infections-in-patients-with-newly-diagnosed-multiple-myelo

DARZALEX + DARZALEX FASPRO - Adverse Event Results - Safety - Infection-Related Events in Part 2 · Infections occurred in 77.5% (n=341) of patients in the DARZALEX monotherapy arm vs 64% ( ...

7. darzalexhcp.com darzalexhcp.com/frontline-dvrd/

Frontline DVRd In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse ...

8. 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 ...