DaraVRD for Multiple Myeloma

Overseen By Susan Bal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Disqualifiers: Poems, Waldenstrom's, Uncontrolled HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DaraVRD, which includes Daratumumab, for multiple myeloma, a type of blood cancer. Researchers aim to determine if early use of this treatment can delay the need for a stem cell transplant. The trial targets individuals recently diagnosed with multiple myeloma who have received minimal prior treatment. Participants should exhibit noticeable signs of the disease, such as specific protein levels in their blood or urine, and generally be in good health otherwise. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the treatment called DaraVRD, which includes the drugs daratumumab, bortezomib, lenalidomide, and dexamethasone, has been used in other studies for multiple myeloma. In a study with 1,249 patients, this treatment was generally well-tolerated. Common side effects included low blood counts and tiredness, but these can often be managed. Serious side effects were less common. The treatment is already approved for multiple myeloma, which adds confidence about its safety. However, as with any medical treatment, discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

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

DaraVRD is unique because it combines four powerful drugs: daratumumab, bortezomib, lenalidomide, and dexamethasone, offering a comprehensive approach to treating multiple myeloma. Unlike other treatments that might use a single or dual-drug regimen, this quadruplet therapy aims to target the cancer cells from multiple angles, potentially leading to better outcomes. Researchers are excited about DaraVRD because daratumumab, a monoclonal antibody, works by directly targeting and destroying myeloma cells, which could enhance the effectiveness of the existing drugs and improve patient responses. This multi-drug combo might offer a more robust treatment option for newly diagnosed patients compared to the standard regimens.

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

Research has shown that a treatment called DaraVRD, which combines four drugs (daratumumab, bortezomib, lenalidomide, and dexamethasone), looks promising for treating multiple myeloma. In earlier studies, this combination worked well, with about 9 out of 10 patients responding positively. The treatment also effectively reduced the number of cancer cells remaining after therapy, indicating good disease control. Overall, evidence suggests that DaraVRD could offer significant benefits for patients newly diagnosed with multiple myeloma. ^{1 6 7 8 9}

Who Is on the Research Team?

Susan Bal, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DaraVRD

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.

How Is the Trial Designed?

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

Quadruplet therapy with DaraVRD in the treatment of newly diagnosed myeloma

DaraVRD is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Multiple myeloma
• Light chain amyloidosis

Approved in United States as Darzalex for:

• Multiple myeloma
• Light chain amyloidosis

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

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]

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]

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]

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]

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. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12003169/

Daratumumab plus bortezomib, lenalidomide and ... These data, together with the phase 3 PERSEUS study, demonstrate the consistent benefit of quadruplet daratumumab plus VRd therapy compared with ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3360/533753/Phase-II-Trial-of-Daratumumab-Bortezomib

Phase II Trial of Daratumumab, Bortezomib, Lenalidomide and ... Conclusions: D-RVD in HR-SMM demonstrates significant activity, including a 98% ORR and high rates of MRD-negative disease, preventing ...

4. darzalex.com darzalex.com/clinical-results/

Clinical Results 91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).

5. nature.com nature.com/articles/s41408-024-01120-9

Quadruplet therapy for newly diagnosed myeloma The combination of lenalidomide, bortezomib, and dexamethasone (RVd) was shown to be highly effective in newly diagnosed myeloma (NDMM) patients ...

6. darzalexhcp.com darzalexhcp.com/frontline-dvrd/

Frontline DVRd - darzalex faspro Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. ... In a pooled safety population of 1249 patients with multiple myeloma (N ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39910273/

the randomized phase 3 CEPHEUS trial - PubMed - NIH This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was ...

8. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/newsroom/new-long-term-progression-free-survival-data-projections-reinforce-subcutaneous-darzalex-daratumumab-quadruplet-therapy-as-a-foundational-standard-of-care-for-patients-with-newly-diagnosed-multiple-myeloma

New long-term progression free survival data projections ... Median progression free survival projected to be 17 years for transplant eligible patients receiving daratumumab-based regimen.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04775550

Study Details | NCT04775550 | DARA RVD For High Risk ... This research study is a Phase II clinical trial, which tests the effectiveness of an investigational drug(s). The investigational drugs used in this research ...