Daratumumab-based Regimen for Multiple Myeloma with Kidney Failure

Overseen By James T Sonnenberg, BS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Augusta University

Disqualifiers: HIV, Hepatitis B, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs, including daratumumab-hyaluronidase, to evaluate their effectiveness for newly diagnosed multiple myeloma patients experiencing kidney failure. The researchers aim to determine how many patients show a strong response to the treatment and whether it improves kidney function after four cycles. The trial also examines whether African American patients respond differently compared to others. It suits those recently diagnosed with multiple myeloma, experiencing kidney issues such as requiring dialysis, and having no allergies to the study drugs. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that the combination of daratumumab-hyaluronidase with cyclophosphamide, bortezomib, and dexamethasone (known as Dara-CyBorD) is generally safe for patients. One study on this combination found that most patients did not experience serious side effects. Common side effects included low blood cell counts and mild injection site reactions, which were manageable.

These drugs have been used in other studies for multiple myeloma and similar conditions, consistently demonstrating safety. Notably, the FDA has approved daratumumab for other uses, indicating it has been tested in many patients and is considered safe for its intended purposes.

Overall, previous studies suggest the treatment is safe, but 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?

Researchers are excited about the Daratumumab-based regimen for multiple myeloma with kidney failure because it combines several powerful elements into one treatment. While the standard care for multiple myeloma often includes drugs like lenalidomide or thalidomide, this new approach uses daratumumab-hyaluronidase, a monoclonal antibody that targets a specific protein on myeloma cells, combined with cyclophosphamide, bortezomib, and dexamethasone. This combination not only aims to enhance the immune system's ability to fight cancer but also offers a new subcutaneous delivery method for daratumumab, which could be more convenient and potentially less daunting for patients compared to intravenous infusions. This innovative mix could improve outcomes, especially for patients with complications like kidney failure.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma with kidney failure?

Research has shown that a treatment combining daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD), which participants in this trial will receive, can be effective for patients with multiple myeloma. Studies have found that this combination improves outcomes, especially for those who cannot undergo transplants. Starting treatment early with daratumumab has also been linked to better kidney health in patients with multiple myeloma and kidney issues. Specifically, one study found that using daratumumab-based therapy improved kidney function in patients with severe kidney problems. This suggests that Dara-CyBorD could help manage multiple myeloma while also addressing kidney damage. ^{1 2 3 6 7}

Who Is on the Research Team?

Amany RA Keruakous, MD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

This trial is for newly diagnosed multiple myeloma patients with new onset renal failure, without allergies to study drugs, good performance status (able to carry out daily activities), and adequate organ function. It's not for those with substance abuse issues, certain infections (HIV, Hepatitis B/C), severe lung or heart conditions, pregnant/breastfeeding women, CNS involvement diseases like plasma cell leukemia or amyloidosis.

Inclusion Criteria

Patients must not have known allergies to any of the study drugs

Your activated partial thromboplastin time is less than 1.5 times the upper limit of normal.

My kidney function is low or I need dialysis.

Exclusion Criteria

You have been diagnosed with HIV, Hepatitis B, or Hepatitis C.

You have another type of cancer that needs treatment at the same time.

Has known substance abuse disorders that would interfere with cooperation with the requirements of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive induction treatment with daratumumab-hyaluronidase (dara SC) in combination with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) for four cycles of 28 days

16 weeks

4 cycles of 28 days each

Restaging

Restaging with repeat PET-CT, bone marrow evaluation, and myeloma serological testing

1-2 weeks

Further Treatment

Further treatment determined by transplant eligibility: additional 2 cycles of Dara-CyBorD followed by maintenance therapy if transplant ineligible, or autologous stem cell transplantation (ASCT) followed by maintenance therapy if transplant eligible

Varies based on treatment path

Maintenance Therapy

Maintenance therapy with lenalidomide and dara SC for 2 years

2 years

Follow-up

Participants are monitored every three months for up to 2 years to assess the duration of response or until disease progression or the start of a new line of therapy

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib, Cyclophosphamide, Dexamethasone
• Daratumumab-hyaluronidase

Trial Overview The study tests a combination of daratumumab-hyaluronidase with bortezomib, cyclophosphamide, and dexamethasone in patients over four cycles. It aims to assess the treatment's effectiveness on kidney function and cancer response rate especially comparing African American patients versus others.

How Is the Trial Designed?

Group I: Dara-CyBorD Experimental Treatment 1 Intervention

Induction treatment with daratumumab-hyaluronidase (dara SC) in combination with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) for four cycles of 28 days, followed by restaging with repeat PET-CT, bone marrow evaluation, and myeloma serological testing.

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a study of 99 Hungarian patients with relapsed/refractory multiple myeloma, daratumumab demonstrated an overall response rate of 88%, with a median progression-free survival (PFS) of 17.0 months, indicating its efficacy in a real-world setting.

The treatment was generally safe, with mild infusion reactions and hematologic toxicities being the most common side effects, and it was effective even in patients with impaired renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients. Lovas, S., Varga, G., Farkas, P., et al.[2020]

In a real-world study of 47 patients with relapsed/refractory multiple myeloma treated with daratumumab, bortezomib, and dexamethasone (DVd), the overall response rate was 78%, indicating that this combination is an effective treatment option.

The treatment was found to be safe, with mostly mild adverse events and no cases leading to permanent drug interruptions, and the median progression-free survival was 10 months, suggesting good durability of response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia. Harvanová, Ľ., Štulajterová, V., Guman, T., et al.[2021]

A 71-year-old woman with refractory multiple myeloma successfully achieved a very good partial response after treatment with a combination of daratumumab, bortezomib, and dexamethasone, demonstrating the efficacy of this regimen in a challenging case.

The treatment was well-tolerated with no infusion-related adverse events, and it led to an improvement in renal function, allowing the patient to reduce her dialysis frequency after 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful management of hemodialysis-dependent refractory myeloma with modified daratumumab, bortezomib and dexamethasone regimen. Mizuno, S., Kitayama, C., Yamaguchi, K., et al.[2022]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

The GMMG-DANTE trial demonstrated that the combination of daratumumab, bortezomib, and dexamethasone (DVd) is effective in treating relapsed or refractory multiple myeloma (MM) patients with severe renal impairment, achieving an overall response rate of 67% among 21 patients.

Despite the patients having severe renal impairment (with a median GFR of 20.1 mL/min), the safety profile of DVd was comparable to that of patients without renal impairment, with manageable toxicities primarily being hematologic and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial. Leypoldt, LB., Gavriatopoulou, M., Besemer, B., et al.[2023]

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]

An 81-year-old woman with multiple myeloma and severe kidney injury was successfully treated with a combination of daratumumab, lenalidomide, and dexamethasone, leading to a rapid 75% reduction in her κ-free light-chain levels within one week.

This case suggests that daratumumab can be an effective treatment option for multiple myeloma patients with acute kidney injury, especially when traditional treatments like bortezomib may pose risks due to heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal recovery following daratumumab, lenalidomide, and dexamethasone therapy in a patient with newly diagnosed dialysis-dependent multiple myeloma. Mizuno, S., Kitayama, C., Mashiko, S., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2468024921009785

RESULTS FROM THE PHASE 3 ANDROMEDA STUDY DARA-VCd increased renal response, with results suggestive of improvement in fatigue-related parameters, such as shortness of breath, feeling tired, or weak.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06142396

Pilot Study Dara-CyBorD in Newly Diagnosed Multiple ... The goal of this study is to assess the efficacy of induction treatment with daratumumab-hyaluronidase (dara SC) with cyclophosphamide, bortezomib, ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/13/3129/536049/Early-daratumumab-therapy-improves-renal-outcomes

Early daratumumab therapy improves renal outcomes in ... We describe the effects of daratumumab-based therapy in 20 patients admitted with a new diagnosis of MM and AKI with a median creatinine of 6.5 mg/dL.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7332897/

Daratumumab plus CyBorD for patients with newly diagnosed ... Application of novel drugs developed for multiple myeloma (MM), and in particular bortezomib, have improved AL amyloidosis outcomes. Among patients at the Mayo ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/14/3721/516083/Daratumumab-cyclophosphamide-bortezomib-and

Daratumumab, cyclophosphamide, bortezomib, and ... In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT220003

Safety run-in results of andromeda. Subcutaneous daratumumab (DARA SC) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients (Pts) with newly diagnosed amyloid light chain ...

7. 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