CyBorD + Daratumumab for Kidney Disease Related to Multiple Myeloma

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Hani Hassoun, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4, CYP1A2 inducers

Disqualifiers: Plasma cell leukemia, AL amyloidosis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Memorial Sloan Kettering Nassau (Limited Protocol Activities) Uniondale, NY

Tufts Medical Center (Data Collection Only) Boston, MA

Weill Cornell Medical Center (Data Collection Only) New York, NY

Mount Sinai Hospital (Data Collection Only) New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center Lead Sponsor

Janssen Pharmaceuticals Industry Sponsor

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] In the phase 3 LEPUS study, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Here, we report updated efficacy and safety results from LEPUS.

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] The multiple myeloma (MM) treatment has changed over the last years due to the introduction of novel drugs. Despite improvements in the MM outcome, MM remains an incurable disease. Daratumumab is a human IgGK monoclonal antibody targeting CD38 with tumor activity associated with immunomodulatory mechanism. In combination with standard of care regimens, including bortezomib (Vd) or lenalidomide (Rd), daratumumab prolonged progression-free survival (PFS) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) and in new diagnosis MM. We report the data of the MM GIMEMA Lazio group in 171 heavily treated pts who received daratumumab, lenalidomide and dexamethasone (DRd) or daratumumab, velcade and dexamethasone (DVd). The overall response rate was 80%, and the overall survival (OS) and PFS were 84% and 77%, respectively. In addition, pts treated with DRd showed a better median PFS compared to pts treated with DVd, at 12 and 24 months, respectively. The most common hematologic treatment-emergent adverse events (TAEs) were neutropenia, thrombocytopenia, and anemia. The most common nonhematologic TAEs were peripheral sensory neuropathy and infections. Our data confirmed that DRd or DVd therapy is effective and safe in RRMM pts, and our real-life analysis could support the physicians regarding the choice of optimal therapy in this setting of pts.

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

Successful management of hemodialysis-dependent refractory myeloma with modified daratumumab, bortezomib and dexamethasone regimen. [2022] A 71-year-old petite Japanese woman was diagnosed with IgG λ-type multiple myeloma with acute kidney injury, severe anemia, and a pathological rib fracture. Emergent hemodialysis was initiated combined with chemotherapy including bortezomib, lenalidomide, and pomalidomide, but myeloma had become refractory due to the treatments. Therefore, a combination therapy with weekly daratumumab (16 mg/kg), bortezomib (0.7 mg/m2), and dexamethasone was started. Daratumumab was administered on a non-dialysis day with a reduced infusion speed to avoid acute water load. No infusion-related adverse events were observed throughout the treatment. Daratumumab and bortezomib were administrated weekly for three times in the first cycle and a hematological very good partial response was achieved. Then, the treatment schedule was reduced to once every three weeks from the 2nd cycle, the very good partial response had been maintained. Fourteen months after the initiation of maintenance hemodialysis, the patient was able to reduce dialysis frequency due to improvement of renal function. A modified daratumumab, bortezomib and dexamethasone regimen could be a valuable treatment option for dialysis-dependent myeloma patients.

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

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021] Intravenous daratumumab (DARZALEX®), a human monoclonal antibody targeting CD38, is approved in the EU and USA for use in combination with bortezomib, thalidomide and dexamethasone for the treatment of adults with newly diagnosed multiple myeloma (MM) who are eligible for autologous stem cell transplantation. A subcutaneous formulation of daratumumab has also been approved in the EU and USA (DARZALEX FASPRO™) for use in MM. In the pivotal phase III CASSIOPEIA trial in adults with newly diagnosed, transplant-eligible MM, the addition of intravenous daratumumab to bortezomib, thalidomide and dexamethasone significantly increased the proportion of patients with a stringent complete response and significantly prolonged progression-free survival; overall survival data are not yet mature. Some facets of health-related quality of life were improved by the addition of daratumumab. The addition of daratumumab had a minimal effect on overall toxicity and the most common grade ≥ 3 adverse events with daratumumab combination therapy were haematological (e.g. neutropenia, lymphopenia). The approval of daratumumab as combination therapy in patients with newly diagnosed, transplant-eligible MM expands the range of MM treatment settings in which daratumumab is an option and the availability of the subcutaneous formulation will likely be of benefit to patients.

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

[Efficacy of bortezomib combined dexamethasone in 24 patients with multiple myeloma]. [2015] Bortezomib, a potent and reversible proteasome inhibitor, induces apoptosis of myeloma cells, resulting in durable responses in patients with multiple myeloma (MM). This study was to explore the medical effects and side effects of bortezomib combined dexamethasone in treating newly diagnosed and relapsed or refractory MM, and evaluate the safety of this regimen in the patients with renal impairment.

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] Daratumumab is a human anti-CD38 monoclonal antibody used in the treatment of refractory and relapsed multiple myeloma. We investigated the efficacy and safety of daratumumab therapy in a real-world setting. Ninety-nine Hungarian patients were included; 48 received monotherapy, while lenalidomide and bortezomib combinations were administered in 29 and 19 cases, respectively. Overall response rate was assessable in 88 patients, with 12 complete, 10 very good partial, 34 partial, and seven minor responses. At a median duration of follow-up of 18.6 months, median progression-free survival (PFS) among all patients was 17.0 months. These values were inferior in the bortezomib combination and monotherapy groups. Patients with early-stage disease (ISS1) had better survival results than those with stage 2 or 3 myeloma (p = 0.009). Heavily pretreated patients had inferior PFS compared to those with 1-3 therapies (p = 0.035). Patients with impaired renal function had PFS results comparable with those having no kidney involvement. There were 10 fatal infections, and the most frequent adverse events were mild infusion-associated reactions and hematologic toxicities. Our results confirm that daratumumab is an effective treatment option for relapsed/refractory MM with an acceptable safety profile in patients with normal and impaired renal function.

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

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. [2021] Intravenous daratumumab (DARZALEX®) is a human CD38 monoclonal antibody approved as combination therapy (with bortezomib, melphalan and prednisone) for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (ASCT). The approval was based on results of the phase 3 ALCYONE trial in which the addition of daratumumab to bortezomib, melphalan and prednisone significantly prolonged median progression-free survival (PFS) relative to bortezomib, melphalan and prednisone alone (primary endpoint). Daratumumab addition was also associated with deeper and durable responses relative to the comparator. The addition of daratumumab did not increase overall toxicity, with the exception of infusion-related reactions and increased rates of infections. The incidences of the most common grade 3 or 4 adverse events in the daratumumab group (neutropenia, thrombocytopenia and anaemia) were largely similar to those in the comparator group. Thus, daratumumab in combination with bortezomib, melphalan and prednisone represents a promising treatment option for patients with NDMM who are ineligible for ASCT.

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] An 81-year-old Japanese woman was diagnosed with Bence Jones protein κ-type multiple myeloma with acute kidney injury and severe anemia, complicated by congestive heart failure with triple vessel coronary artery disease. Her serum κ-free light-chain (FLC) level was 49,400 mg/L and κ/λ ratio was extremely high at 2373. Her kidney function deteriorated rapidly and required hemodialysis before initiating chemotherapy. A combination therapy of daratumumab (16 mg/kg), lenalidomide, and dexamethasone was initiated as a first-line treatment; the infusion rate of daratumumab was adjusted to reduce the heart load. The level of κ-FLC was rapidly reduced by 75% in only one week and by 99% after three weeks. Furthermore, she was dialysis-independent after the fourth dose of daratumumab. We report the first case of untreated patient with myeloma who had been successfully treated with daratumumab, lenalidomide, and dexamethasone therapy even in dialysis requiring state. Daratumumab may benefit patients with acute kidney injury caused by multiple myeloma, owing to the immediate need of FLC level reduction. Daratumumab and lenalidomide combination therapy could be a valuable treatment option for patients requiring dialysis when bortezomib may be hesitate to use due to severe heart disease.