Daratumumab After Stem Cell Transplant for Multiple Myeloma

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

31 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Daratumumab for multiple myeloma?

Daratumumab, when used in combination with other drugs, has been shown to significantly improve patient outcomes in multiple myeloma, such as increasing the rate of complete response and prolonging the time patients live without the disease getting worse. This has been demonstrated in several clinical trials, including the CASSIOPEIA and ALCYONE trials. ^{1 2 3 4 5}

Is daratumumab safe for use in humans?

Daratumumab, also known as Darzalex, has been shown to have an acceptable safety profile in multiple studies for treating multiple myeloma. Common side effects include low blood cell counts and infusion-related reactions, but it generally does not increase overall toxicity when used in combination with other treatments. ^{1 3 4 6 7}

How does the drug daratumumab differ from other treatments for multiple myeloma?

Daratumumab is unique because it is a monoclonal antibody that specifically targets CD38, a protein found on multiple myeloma cells, and it can be used both as a monotherapy and in combination with other drugs. It works through several mechanisms, including directly killing cancer cells and modifying the immune system, and is available in both intravenous and subcutaneous forms, offering flexibility in administration. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies how well daratumumab after a stem cell transplant works in treating patients with multiple myeloma. Monoclonal antibodies, such as daratumumab, may kill cancer cells that are left after chemotherapy.

Research Team

Amrita Y. Krishnan

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

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)

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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 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]

References

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

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

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

Daratumumab: First Global Approval. [2018]

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

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

4. Spain pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Impact of daratumumab on stem cell mobilization and collection, engraftment and early post-transplant complications among multiple myeloma patients undergoing autologous stem cell transplantation. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety Analysis of Five Randomized Controlled Studies of Daratumumab in Patients With Multiple Myeloma. [2021]