CyBorD + Daratumumab for Kidney Disease Related to Multiple Myeloma

Recruiting at 10 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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of drugs—bortezomib (Velcade), cyclophosphamide, dexamethasone, and daratumumab (Darzalex)—can safely and effectively treat kidney disease related to multiple myeloma, a type of blood cancer. It specifically examines kidney issues like cast nephropathy, where certain proteins block the kidneys. The trial consists of two parts: one for individuals with cast nephropathy and another for those with other kidney diseases linked to similar protein issues. Suitable participants have a confirmed kidney problem related to multiple myeloma and measurable protein levels in their blood or urine. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the treatment combination of cyclophosphamide, bortezomib, dexamethasone, and daratumumab (often called CyBorD-Dara) is generally well-tolerated by patients. One study found that 72% of patients completed nine cycles of treatment without severe nerve damage. This indicates that many people handle the treatment well, with few serious side effects related to nerve health.

While some side effects may occur, the absence of severe nerve issues in most patients is encouraging. Prospective trial participants might find this information reassuring regarding its safety. Always consult your doctor about any concerns or questions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of CyBorD (Bortezomib, Cyclophosphamide, and Dexamethasone) with Daratumumab for kidney disease related to multiple myeloma because it introduces a new way to tackle the condition. Unlike standard treatments that often focus solely on controlling the myeloma, this approach integrates Daratumumab, an antibody that targets a specific protein on myeloma cells, which may enhance the treatment's effectiveness. Additionally, the subcutaneous administration of Daratumumab is more convenient and potentially leads to fewer side effects compared to traditional intravenous methods. This combination could offer a more comprehensive treatment option, especially for patients who struggle with the typical side effects of existing therapies.

What evidence suggests that this trial's treatments could be effective for kidney disease related to multiple myeloma?

Research has shown that adding daratumumab to the CyBorD treatment plan (which includes cyclophosphamide, bortezomib, and dexamethasone) can improve outcomes for patients with multiple myeloma. In this trial, participants will join different arms based on their specific kidney disease related to multiple myeloma. Arm A will include patients with cast nephropathy, while Arm B will include all other MGRS-associated diseases, excluding AL amyloidosis. This combination is particularly effective for those with kidney problems caused by multiple myeloma. Using daratumumab early in treatment has been linked to improved kidney function. Additionally, the CyBorD-Dara combination has significantly reduced cancer cells, with many patients achieving very low levels. This suggests that the treatment could effectively address kidney issues related to multiple myeloma. ^{1 6 7 8 9}

Who Is on the Research Team?

Hani Hassoun, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06083922

NCT06083922 | A Study of CyBorD (Cyclophosphamide, ... The purpose of this study is to find out whether cyclophosphamide, bortezomib, dexamethasone (CyBorD) with daratumumab SC is a safe treatment combination ...

2. 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 regimens. ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/429015

A Study of CyBorD (Cyclophosphamide, Bortezomib ... The purpose of this study is to find out whether cyclophosphamide, bortezomib, dexamethasone (CyBorD) with daratumumab SC is a safe ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12242421/

Early daratumumab therapy improves renal outcomes in ... Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury - PMC.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265022002312

CyBorD-DARA in Newly Diagnosed Transplant-Eligible ... CyBorD-DARA is an effective and well-tolerated regimen in transplant-eligible NDMM, achieving MRD negativity at the end of maintenance in 70% of patients.

6. 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

7. jnj.com jnj.com/media-center/press-releases/johnson-johnson-reinforces-its-leadership-in-hematology-at-ash-2025-unveiling-new-paradigm-shifting-research

Johnson & Johnson reinforces its leadership in hematology ... For newly diagnosed multiple myeloma in transplant candidates, the NCCN® guidelines recommend daratumumab in combination with bortezomib, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04166565?tab=table

NCT04166565 | Daratumumab Combined With Bortezomib ... Daratumumab Combined With Bortezomib, Cyclophosphamide and Dexamethasone for the Treatment of Multiple Myeloma Patients Presenting With Extramedullary Disease.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430984/

P872: EFFICACY OF DARATUMUMAB PLUS ... To present interim results on the efficacy/safety of daratumumab (Dara) plus bortezomib (V), cyclophosphamide (C) and dexamethasone (D) in patients (pts) with ...