Daratumumab Combination Therapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arkansas

Disqualifiers: Hypertension, Diabetes, Hepatitis, 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 tests whether adding daratumumab, a new treatment, to a combination of therapies helps people with multiple myeloma live longer with fewer side effects. Multiple myeloma is a type of blood cancer affecting plasma cells in the bone marrow. The trial seeks individuals recently diagnosed with active multiple myeloma requiring treatment and who have not undergone more than four cycles of prior therapy. Participants should have high-risk disease, indicating a more aggressive cancer that needs a stronger treatment approach. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that daratumumab, a drug for multiple myeloma, is usually well-tolerated by patients. When included in a treatment plan, it can lead to significant and lasting improvements. However, awareness of possible side effects is important. For instance, upper respiratory tract infections are a common side effect when taking daratumumab alone.

In one study, about 77.5% of patients using daratumumab alone reported infections. Although this number might seem high, these infections are often manageable. Overall, daratumumab has proven effective and offers promising results for people with multiple myeloma. Discussing any concerns with a doctor is advisable to understand the possible side effects and how they can be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Daratumumab combination therapy for multiple myeloma is unique because it integrates an innovative approach of using daratumumab in multiple stages of treatment, including induction, consolidation, and maintenance phases. Unlike traditional treatments that focus primarily on chemotherapy or stem cell transplants, this method leverages daratumumab's ability to target CD38 on myeloma cells, enhancing the immune system's response against the cancer. By alternating daratumumab with other drugs like carfilzomib and lenalidomide, this regimen introduces a strategic layering of therapies that could potentially improve patient outcomes by reducing the likelihood of resistance and relapse. Researchers are excited about this approach as it combines the strengths of existing treatments with novel immunological strategies, potentially offering more effective management of multiple myeloma.

What evidence suggests that daratumumab combination therapy could be effective for multiple myeloma?

Research has shown that daratumumab effectively treats multiple myeloma, a type of blood cancer. In this trial, participants will receive a combination therapy that includes daratumumab. Studies have found that a treatment plan with daratumumab can help 95% of patients eligible for a stem cell transplant avoid cancer progression for four years. In another study, daratumumab achieved a 91.7% overall response rate by the end of a specific treatment phase. For newly diagnosed patients eligible for transplants, combining daratumumab with other treatments resulted in a 100% response rate. These findings suggest that adding daratumumab to a treatment plan may help patients live longer with fewer side effects. ^{1 2 6 7 8}

Who Is on the Research Team?

Frits van Rhee

Principal Investigator

University of Arkansas for Medical Science-Myeloma Institute

Are You a Good Fit for This Trial?

Adults aged 18-75 with newly diagnosed active Multiple Myeloma requiring treatment, who haven't had more than four cycles of MM therapy. Must have high-risk disease indicators like a specific risk score or primary plasma cell leukemia, adequate organ function, and agree to use contraception if of childbearing potential.

Inclusion Criteria

I can care for myself, but my movement may be limited due to bone disease from multiple myeloma.

My kidney function and liver enzymes are within the required limits.

My condition is considered high-risk due to specific test results or diagnosis.

Exclusion Criteria

I haven't had cancer before, except for certain skin cancers or cervical cancer that's been treated, or any other cancer I haven't been treated for in the last year.

Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration.

My condition is not considered high-risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy with Carfilzomib, Thalidomide, Dexamethasone, Daratumumab, CisPlatin, Adriamycin, Cyclophosphamide, and Etoposide

8-12 weeks

Autologous Stem Cell Transplant (ASCT) 1

Participants undergo the first autologous stem cell transplant with Melphalan and Dexamethasone

4 weeks

Immunological Consolidation 1

Participants receive immunological consolidation with Daratumumab

4 weeks

Consolidation 1

Participants receive consolidation therapy with Daratumumab, Carfilzomib, and Dexamethasone

4 weeks

ASCT 2 (optional)

Participants may undergo a second autologous stem cell transplant with Melphalan and Dexamethasone

4 weeks

Immunological Consolidation 2

Participants receive a second round of immunological consolidation with Daratumumab

4 weeks

Maintenance

Participants receive maintenance therapy alternating between Dara-KD and Dara-RD in 3-month blocks

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The trial is testing the addition of daratumumab to the Total Therapy approach for multiple myeloma. It aims to see if this new combination helps patients live longer with fewer side effects compared to current treatments.

How Is the Trial Designed?

Group I: Study Treatment Experimental Treatment 12 Interventions

Induction Chemotherapy: Carfilzomib, Thalidomide, Dexamethasone, Daratumumab , CisPlatin, Adriamycin, Cyclophosphamide and Etoposide (KTD-Dara-PACE). Autologous Stem Cell Transplant (ASCT) 1: Melphalan, Dexamethasone, ASCT. Immunological Consolidation 1: Daratumumab. Consolidation 1: Daratumumab, Carfilzomib, Dexamethasone (Dara-KD). ASCT 2 (optional): Melphalan, Dexamethasone, ASCT. Immunological Consolidation 2: Daratumumab. Maintenance: Dara-KD alternating with Daratumumab, lenalidomide, and Dexamethasone (Dara-RD) in 3-month blocks. Bortezomib may be substituted for carfilzomib throughout the regimen at the discretion of the treating physician.

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

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 ...