Daratumumab + Bortezomib + Dexamethasone for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eastern Cooperative Oncology Group

Must not be taking: Anti-CD38 antibodies

Disqualifiers: Pregnancy, Uncontrolled asthma, Cardiac disease, 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

Compensation: Varies

Number of Visits: 7

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding daratumumab-hyaluronidase (an injection) to the usual treatment can improve kidney function in individuals with newly diagnosed multiple myeloma and kidney failure. Participants will receive either the new medication combination or the standard treatment for four months. Researchers will monitor their health for up to 10 years to check for side effects and track their condition. This trial suits those diagnosed with multiple myeloma and kidney failure within the last 90 days. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

Research has shown that the combination of daratumumab, bortezomib, and dexamethasone is generally well-tolerated by patients with multiple myeloma. One study found that adding daratumumab to the other two drugs significantly improved patient outcomes without increasing severe side effects. Most side effects were manageable and similar to those experienced with only bortezomib and dexamethasone. Another study confirmed the treatment's long-term safety, with no unexpected harmful effects emerging over time. This suggests the treatment is safe for humans, although individual experiences may vary. ^{1 2 3 4 5}

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

Researchers are excited about Daratumumab-Bortezomib-Dexamethasone (Dara-Bor-Dex) for treating multiple myeloma because this combination introduces daratumumab, a monoclonal antibody, which targets a specific protein on cancer cells, potentially offering a more precise attack than standard treatments. Unlike traditional regimens like Cyclophosphamide-Bortezomib-Dexamethasone (Cy-Bor-Dex), Dara-Bor-Dex leverages daratumumab's ability to directly engage the immune system, enhancing the body's natural defenses against myeloma cells. This targeted approach might improve patient outcomes by offering enhanced efficacy and possibly reducing side effects compared to the broader action of conventional chemotherapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma with kidney failure?

This trial will compare two treatment regimens for multiple myeloma. In one arm, participants will receive a combination of Daratumumab, Bortezomib, and Dexamethasone (Dara-Bor-Dex). Studies have shown that adding Daratumumab to the standard treatment of Bortezomib and Dexamethasone significantly benefits patients with multiple myeloma. Research indicates that this combination increases survival chances and reduces the risk of death compared to using Bortezomib and Dexamethasone alone. Patients receiving this combination also experience longer periods before their cancer worsens. The overall response rate, which measures how well the cancer shrinks or disappears, improves with the addition of Daratumumab. These findings suggest that Daratumumab enhances the effectiveness of standard multiple myeloma treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Amany Keruakous

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults (18+) who have just been diagnosed with multiple myeloma and are experiencing kidney failure. Participants must be well enough to do daily activities, though some may have limited activity due to bone pain or fractures from cancer.

Inclusion Criteria

My lung function is at least 50% of normal despite recent respiratory disease.

My heart condition is stable and I have only mild or no symptoms with normal activity.

I am able to care for myself, or my limited activity is due to bone pain or fractures from cancer.

Exclusion Criteria

Patients living outside the US are excluded

I do not have smoldering myeloma or monoclonal gammopathy of undetermined significance.

I have never had a lymphoproliferative disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either daratumumab-bortezomib-dexamethasone or cyclophosphamide-bortezomib-dexamethasone for 4 cycles

16 weeks

4 cycles (each cycle is 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 months for years 1-2, then every 6 months for years 3-10

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab-hyaluronidase
• Dexamethasone

Trial Overview

The study compares two treatments for newly diagnosed multiple myeloma with kidney failure: one group gets daratumumab-hyaluronidase, bortezomib, and dexamethasone; the other gets cyclophosphamide, bortezomib, and dexamethasone. Treatment lasts four months by random assignment.

How Is the Trial Designed?

Group I: ARM B (Dara-Bor-Dex) Experimental Treatment 3 Interventions

Daratumumab-Bortezomib-Dexamethasone

Group II: ARM A (Cy-Bor-Dex) Active Control 3 Interventions

Cyclophosphamide-Bortezomib-Dexamethasone (4 cycles)

Who Is Running the Clinical Trial?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10022857/

Overall Survival With Daratumumab, Bortezomib, and ... - PMC

At a median follow-up of 72.6 months, D-Vd significantly prolonged OS, with a 26% reduction in the risk of death versus bortezomib and dexamethasone alone ( ...

2.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/7081/527410/Efficacy-and-Safety-of-Daratumumab-Combined-with

Efficacy and Safety of Daratumumab Combined with ...

The addition of daratumumab to Vd significantly increase the remission rate, deepen the depth of remission, and improve the poor prognosis in NDMM patients ...

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1606038

Daratumumab, Bortezomib, and Dexamethasone for ...

Daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone.

4.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO.21.02734

Overall Survival With Daratumumab, Bortezomib, and ...

Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10526417/

Daratumumab, Bortezomib, and Dexamethasone for ... - PMC

The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497118611218

Efficacy and Safety of Daratumumab, Bortezomib ...

In phase 3 studies, DARA-based regimens reduced the disease progression or death risk by ≥44%, nearly doubled the rates of complete response (CR) or better, and ...

7.

myeloma.org

myeloma.org/videos/two-year-update-castor-efficacy-safety-daratumumab-bortezomib-dexamethasone-versus

2 Year Update of Castor | Int'l Myeloma Fndn

Two-Year Update of Castor: Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in First ...