Daratumumab-based Regimen for Multiple Myeloma with Kidney Failure
Recruiting in Palo Alto (17 mi)
Overseen byAmany RA Keruakous, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Augusta University
Disqualifiers: HIV, Hepatitis B, COPD, others
No Placebo Group
Breakthrough Therapy
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?
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.12567
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.
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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.
See 7 more
Trial 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 (Other)
- Daratumumab-hyaluronidase (Monoclonal Antibodies)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Dara-CyBorDExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Georgia Cancer Center-Augusta UniversityAugusta, GA
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Who Is Running the Clinical Trial?
Augusta UniversityLead Sponsor
Janssen Scientific Affairs, LLCIndustry Sponsor
References
[The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment]. [2023]To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).
Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia. [2021]Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. >2 prior treatments, with equally good effectivity in standard-risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.
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.
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]Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR <30 mL/min/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55-89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4-27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1-10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI.
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.
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.
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.