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

Trial Summary

What is the purpose of this trial?

The goal of this study is to assess the efficacy of induction treatment with daratumumab-hyaluronidase (dara SC) with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) for four cycles in patients with newly diagnosed multiple myeloma who have new onset renal failure. This study will also investigate the difference responses in African American (AA) patients versus non-African American patients. The primary questions this study aims to answer are: 1. To evaluate the very good partial response rate (VGPR) after 4 cycles of Dara-CyBord. 2. To evaluate the renal response rate (RRR) after 4 cycles of Dara-CyBord.

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.

What data supports the effectiveness of the drug Daratumumab-based Regimen for Multiple Myeloma with Kidney Failure?

Research shows that a combination of daratumumab, bortezomib, and dexamethasone is effective for patients with multiple myeloma and severe kidney issues, achieving a 67% overall response rate in a trial and improving kidney function in some cases. ^{1 2 3 4 5}

What makes the daratumumab-based drug regimen unique for treating multiple myeloma with kidney failure?

This treatment is unique because it combines daratumumab, a monoclonal antibody targeting CD38, with bortezomib, cyclophosphamide, and dexamethasone, specifically for patients with multiple myeloma and kidney failure. It has shown effectiveness in improving kidney function and maintaining a good response in patients who are dependent on dialysis, offering a valuable option for those with severe kidney impairment. ^{1 2 5 6 7}

Research Team

Amany RA Keruakous, MD

Principal Investigator

Augusta University

Eligibility Criteria

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.

I haven't had serious heart issues or unstable heart conditions in the last 6 months.

I have severe nerve damage in my hands or feet.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

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

2. Slovakia pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

Renal recovery following daratumumab, lenalidomide, and dexamethasone therapy in a patient with newly diagnosed dialysis-dependent multiple myeloma. [2022]

4. Switzerland 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. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

Successful management of hemodialysis-dependent refractory myeloma with modified daratumumab, bortezomib and dexamethasone regimen. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients. [2020]

7. United States 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. [2022]