Daratumumab After Stem Cell Transplant for Multiple Myeloma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Organ transplant, Infection, Autoimmune, 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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug called daratumumab in treating multiple myeloma, a type of blood cancer, after patients undergo a stem cell transplant. Daratumumab, a monoclonal antibody, may help eliminate any remaining cancer cells. Participants will receive daratumumab treatments on a set schedule for up to 24 months. The trial seeks individuals with multiple myeloma who have already received initial treatment and plan to undergo a standard stem cell transplant. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 be on chemotherapy, biologic, or hormonal therapy for cancer treatment while participating. It's best to discuss your specific medications with the trial team.

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

Research has shown that daratumumab is usually well-tolerated for treating multiple myeloma. One study found that using daratumumab alone had effects similar to its use in combination with other treatments. However, infections commonly occurred as a side effect, affecting many patients. The most frequent infections involved the upper respiratory tract, including the nose and throat. Despite these common side effects, patients taking daratumumab generally demonstrated a high survival rate. This suggests that, despite some risks, the treatment is relatively safe for many people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Daratumumab is unique because it targets CD38, a protein highly expressed on multiple myeloma cells, which helps the immune system attack and destroy these cancer cells. Unlike the standard treatments that typically involve chemotherapy and stem cell transplants, daratumumab is a monoclonal antibody, offering a more targeted approach. Researchers are excited about daratumumab because it has shown promise in enhancing the effectiveness of traditional therapies, potentially leading to longer remission periods and improved patient outcomes. This targeted action not only aims to be more effective but also might come with fewer side effects compared to conventional chemotherapy.

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

Research has shown that daratumumab effectively treats multiple myeloma, a type of blood cancer. One study found that 95% of patients eligible for a stem cell transplant did not experience disease progression for four years. Another study reported that 91.7% of patients responded well to the treatment. In this trial, participants will receive daratumumab following a stem cell transplant, administered through an IV. These findings suggest that daratumumab can significantly aid in managing multiple myeloma after a stem cell transplant. ^{1 2 6 7 8}

Who Is on the Research Team?

Amrita Y. Krishnan

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma who have adequate organ function, no severe asthma or uncontrolled diseases, and are not pregnant. They must understand the study and agree to use birth control. Participants should be within 2-13 months of their first therapy for multiple myeloma and have a sufficient number of stem cells collected for transplant.

Inclusion Criteria

I am scheduled for a stem cell transplant with a specific chemotherapy dose, adjusted for my kidney function.

My organs are strong enough for high dose chemotherapy and a stem cell transplant.

I have been diagnosed with multiple myeloma, amyloidosis included.

Exclusion Criteria

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

I've been cancer-free for 5 years, except for minor skin cancers or early-stage prostate or breast cancer.

You have known allergies or sensitivity to certain types of medications made from human proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive daratumumab intravenously every week for 8 weeks, every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The trial tests daratumumab's effectiveness following a stem cell transplant in treating multiple myeloma. Daratumumab is an antibody that may destroy remaining cancer cells post-chemotherapy. The study includes autologous stem cell transplantation, melphalan chemotherapy, and biomarker analysis.

How Is the Trial Designed?

Group I: Treatment (ASCT, melphalan, daratumumab) Experimental Treatment 4 Interventions

Patients undergo standard of care ASCT with a conditioning regimen of melphalan. Beginning 60-120 days after ASCT, patients receive daratumumab IV every week for 8 weeks, every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Daratumumab, a monoclonal antibody targeting CD38, has shown significant anti-myeloma activity through various mechanisms, including direct apoptosis and immune system modulation, making it a key treatment for relapsed-refractory multiple myeloma (RRMM).

Clinical trials, such as CASTOR and POLLUX, demonstrated that daratumumab in combination with other therapies (like bortezomib and lenalidomide) significantly improves overall response rates and progression-free survival compared to standard treatments, leading to its approval and integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Offidani, M., Corvatta, L., Morè, S., et al.[2021]

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 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 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]

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 ...