Daratumumab Combination for Multiple Myeloma

Overseen By Muzaffar Qazilbash

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of treatments, including daratumumab and pomalidomide, can effectively manage multiple myeloma that has returned after a stem cell transplant. Daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) is an antibody designed to block cancer cell growth, while pomalidomide is a chemotherapy drug that aims to stop cancer cells from spreading. Suitable participants are those whose multiple myeloma has returned after a stem cell transplant and who have responded to some form of follow-up therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

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

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

Research has shown that daratumumab, when combined with hyaluronidase-fihj, is as effective as the traditional IV form for treating multiple myeloma. Patients generally tolerate this combination well. However, 77.5% of those taking daratumumab alone experienced infections, most commonly upper respiratory infections. Despite these side effects, the treatment is generally considered safe, as it has been used for other conditions and offers a good balance of benefits and risks for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Daratumumab is unique because it targets a specific protein called CD38 on the surface of multiple myeloma cells, which is different from most standard treatments that often focus on killing rapidly dividing cells in general. This targeted approach not only helps to directly attack the cancer cells but also aids the immune system in recognizing and destroying them. Researchers are excited about daratumumab because it offers a novel mechanism of action that could improve patient outcomes and potentially reduce some of the side effects associated with broader chemotherapy treatments.

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

Research has shown that daratumumab, when combined with hyaluronidase-fihj, effectively treats multiple myeloma. In earlier studies, a treatment plan with these two drugs resulted in 95% of newly diagnosed patients who had a transplant not experiencing disease progression for four years. Another study found that 91.7% of patients responded positively by the end of their treatment. These findings suggest that daratumumab effectively manages multiple myeloma, especially when other treatments have failed. Participants in this trial will receive daratumumab as part of their treatment regimen. ^{1 2 6 7 8}

Who Is on the Research Team?

Muzaffar Qazilbash, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with relapsed multiple myeloma post-stem cell transplant. They must have had a partial response to salvage therapy, be within 60-180 days post-transplant, and have an ECOG status of 0-2. Key eligibility includes adequate kidney function (creatinine <= 2.5 mg/dL), platelet count >= 50,000/mm^3, neutrophil count >= 1000/mm^3, liver enzymes up to three times the normal limit, and no uncontrolled heart arrhythmias.

Inclusion Criteria

Your liver enzyme levels are not more than three times the normal limit.

My condition worsened after initial treatment but improved with further therapy.

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

Exclusion Criteria

I have not had radiotherapy in the last 14 days.

I am currently pregnant or breastfeeding.

I have tested positive for hepatitis B surface antigen or have resolved hepatitis B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and hyaluronidase-fihj subcutaneously and pomalidomide orally in cycles every 28 days for up to 3 years

3 years

Frequent visits during initial cycles, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks after initial follow-up at 30 and 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The study tests daratumumab with hyaluronidase-fihj and pomalidomide in treating relapsed multiple myeloma after stem cell transplant. Daratumumab is designed to stop cancer cells from growing by targeting specific proteins on their surface while pomalidomide aims to kill or halt the division of cancer cells.

How Is the Trial Designed?

Group I: Treatment (daratumumab) Experimental Treatment 1 Intervention

Beginning 60-120 days after transplant, participants receive daratumumab IV over 4-8 hours on days 1, 8, 15 and 22 of courses 1 and 2 and days 1 and 15 of courses 3-6, then on day 1 of subsequent courses. Courses repeat every 28 days for 3 years 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.

Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]

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]

In the POLLUX study, after 25.4 months of follow-up, the combination of daratumumab with lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma, with a hazard ratio of 0.41 compared to lenalidomide/dexamethasone alone.

The overall response rate was notably higher with the daratumumab combination (92.9%) compared to the control (76.4%), and a significant proportion of patients achieved minimal residual disease negativity (26.2% vs 6.4%), indicating a deeper response without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Dimopoulos, MA., San-Miguel, J., Belch, A., et al.[2019]

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]

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, 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, 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 ...