DaraVRD for Multiple Myeloma

Overseen By Susan Bal, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Alabama at Birmingham

Disqualifiers: Poems, Waldenstrom's, Uncontrolled HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a high-tech test to check for tiny amounts of leftover cancer cells in patients with newly diagnosed multiple myeloma. If no cancer cells are found, doctors might delay a major treatment called stem cell transplant. This approach aims to avoid the severe side effects of the transplant if it's not needed.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have been on certain treatments like dexamethasone, bortezomib, or cyclophosphamide for acute symptoms, you may need to stop them before enrolling.

What data supports the effectiveness of the drug DaraVRD for treating multiple myeloma?

Daratumumab, a key component of DaraVRD, has shown to be effective in treating multiple myeloma by increasing the proportion of patients with a complete response and prolonging the time patients live without the disease getting worse. It has been effective both as a single drug and in combination with other treatments, showing deep and lasting responses in patients. ^{1 2 3 4 5}

Is DaraVRD (Daratumumab) safe for humans?

Daratumumab, also known as Darzalex or Darzalex Faspro, has been shown to have an acceptable safety profile in clinical trials for multiple myeloma. Common side effects include low blood cell counts (neutropenia, thrombocytopenia, anemia), pneumonia, and infusion-related reactions, but it is generally considered safe when used as directed. ^{1 4 5 6 7}

How is the drug DaraVRD different from other treatments for multiple myeloma?

DaraVRD, which includes daratumumab, is unique because it targets a specific protein (CD38) on multiple myeloma cells, leading to their destruction through various immune system mechanisms. It can be used both as a single agent and in combination with other drugs, offering a novel option for patients who have not responded to other treatments. ^{1 2 4 5 6}

Research Team

Susan Bal, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who haven't had much prior treatment. They must be expected to live at least a year, have good organ function, and agree to use contraception. It's important they can follow the study rules and are fit enough for stem cell transplant. At least 30% of participants will be ethnic/racial minorities.

Inclusion Criteria

At least 30% of people from different ethnic or racial backgrounds will be included in the study. If needed, the enrollment of people from other backgrounds may be paused to make sure that at least 30% of ethnic minorities are included.

I agree to use birth control and undergo pregnancy tests if required.

I've only had short-term treatment for my multiple myeloma symptoms.

Exclusion Criteria

I have severe nerve pain or damage.

I have had a stroke before or a temporary blockage of blood flow to my brain in the last year.

I haven't had major surgery, radiotherapy, or needed treatment for an infection in the last 14 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Quadruplet therapy with Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DaraVRD) in the treatment of newly diagnosed myeloma

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Treatment Details

Interventions

• DaraVRD (Monoclonal Antibodies)

Trial Overview The MILESTONE trial is testing if using next-generation sequencing to check for minimal residual disease can help decide whether patients with new multiple myeloma can wait before having a stem cell transplant. The intervention being tested is DaraVRD.

Participant Groups

Group I: Induction - Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DaraVRD) Experimental Treatment 1 Intervention

Quadruplet therapy with DaraVRD in the treatment of newly diagnosed myeloma

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

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]

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]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[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]

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 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]

In a study of 15 multiple myeloma patients with renal impairment, daratumumab-based treatments showed a high overall response rate of 91%, indicating strong efficacy in this patient group.

The treatment was generally safe, with the most common side effects being mild neutropenia and infusion-related reactions, suggesting that daratumumab can be a viable option for managing multiple myeloma in patients with kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment]. Yin, LL., Shen, YL., Min, FL., et al.[2023]

References

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

Daratumumab: First Global Approval. [2018]

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

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]

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

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]

7. China pubmed.ncbi.nlm.nih.gov

[The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment]. [2023]