CyBorD + Daratumumab for Kidney Disease Related to Multiple Myeloma

Recruiting at 9 trial locations

Overseen By Carlyn R Tan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4, CYP1A2 inducers

Disqualifiers: Plasma cell leukemia, AL amyloidosis, 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: Unknown

Duration: 8 cycles

61 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether cyclophosphamide, bortezomib, dexamethasone (CyBorD) with daratumumab SC is a safe treatment combination for MGRS-associated kidney disease including cast nephropathy associated with multiple myeloma. In addition, the researchers will find out whether the study drug combination is an effective treatment for these conditions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use strong CYP3A4 and CYP1A2 inducers or inhibitors while participating in the study.

What data supports the effectiveness of the drug combination CyBorD + Daratumumab for kidney disease related to multiple myeloma?

Research shows that a combination of daratumumab, bortezomib, and dexamethasone can lead to significant clinical benefits in patients with multiple myeloma, including improved kidney function and prolonged progression-free survival. In one case, a patient with multiple myeloma and kidney issues experienced improved kidney function and reduced dialysis frequency after treatment with daratumumab, bortezomib, and dexamethasone. ^{1 2 3 4 5}

Is the combination of CyBorD and Daratumumab safe for treating kidney disease related to multiple myeloma?

The combination of bortezomib (Velcade), cyclophosphamide (Cytoxan), and daratumumab (Darzalex) has been studied for multiple myeloma and is generally considered safe, though common side effects include blood-related issues like neutropenia (low white blood cell count) and anemia, as well as infections and mild infusion reactions. These treatments have been used in patients with normal and impaired kidney function, showing an acceptable safety profile. ^{2 4 5 6 7}

How is the CyBorD + Daratumumab drug different from other drugs for kidney disease related to multiple myeloma?

The CyBorD + Daratumumab drug is unique because it combines multiple medications, including daratumumab, which targets a specific protein (CD38) on myeloma cells, and is effective even in patients with kidney issues. This combination can improve kidney function and reduce the need for dialysis, offering a novel approach for patients with multiple myeloma-related kidney disease. ^{2 3 4 6 8}

Research Team

Hani Hassoun, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with a specific kidney disease linked to abnormal protein production (MGRS) and related conditions. Participants must have certain levels of kidney function, no recent exposure to nephrotoxic substances, and be able to follow the study plan. Pregnant or breastfeeding women, those with other serious health issues like HIV or severe lung disease, or who've had certain treatments recently can't join.

Inclusion Criteria

My kidney disease related to MGRS was confirmed by a biopsy.

I am mostly active and can care for myself.

I haven't been exposed to kidney-damaging substances recently.

Exclusion Criteria

You have received or are currently receiving experimental drugs for the treatment of plasma cell disorders.

My cancer has spread to my brain or spinal cord.

I have been treated for a disorder affecting my plasma cells.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8 cycles of CyBorD-Dara SC, with treatment left to the discretion of the treating physician. Eligible patients may undergo ASCT after 8 cycles.

8 cycles

Maintenance

Ineligible ASCT patients continue maintenance Bortezomib/Dexamethasone every other week with daratumumab SC every 4 weeks for 2 years.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Bortezomib
• Cyclophosphamide
• Daratumumab
• Dexamethasone

Trial Overview Researchers are testing if combining cyclophosphamide, bortezomib, dexamethasone (CyBorD), and daratumumab is safe and effective for treating MGRS-associated kidney disease. The study will assess this combination's impact on patients' condition by monitoring their response to treatment.

Participant Groups

Group I: Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis Experimental Treatment 4 Interventions

Planned 8 cycles of CyBorD-Dara SC, treatment will be left to the discretion of the treating physician. It is recommended that patients eligible for ASCT undergo ASCT after 8 cycles of induction and that patient ineligible for ASCT, continue maintenance Bortezomib/Dexamethasone administered every other week with daratumumab SC administered every 4 weeks, for a period of 2 years from start of treatment.

Group II: Arm A will include patients with cast nephropathy Experimental Treatment 4 Interventions

Planned 8 cycles of CyBorD-Dara SC, treatment will be left to the discretion of the treating physician. It is recommended that patients eligible for ASCT undergo ASCT after 8 cycles of induction and that patient ineligible for ASCT, continue maintenance Bortezomib/Dexamethasone administered every other week with daratumumab SC administered every 4 weeks, for a period of 2 years from start of treatment.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Findings from Research

In the phase 3 LEPUS study involving 211 Chinese patients with relapsed or refractory multiple myeloma, the combination of daratumumab, bortezomib, and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) compared to bortezomib and dexamethasone alone (median PFS of 14.8 months vs. 6.3 months).

D-Vd also showed higher overall response rates and better response quality, with 84.7% of patients achieving an overall response compared to 66.7% with Vd, and no new safety concerns were identified, supporting D-Vd as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. Fu, W., Li, W., Hu, J., et al.[2023]

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]

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]

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]

In a study of 24 multiple myeloma patients treated with bortezomib and dexamethasone, 79.2% showed a positive response, with a notably higher complete remission rate in light-chain type patients (57.1%) compared to non-light-chain type patients (5.9%).

The treatment was found to be safe for patients with renal impairment, as their renal function improved during chemotherapy, and the adverse events were manageable, with most patients tolerating the side effects well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. Li, J., Zhao, Y., Luo, SK., et al.[2015]

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]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. [2023]

2. 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]

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

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

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

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

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. [2015]

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

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

8. 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]