Testing the Investigational Agent Combination of Daratumumab, Bortezomib, and Dexamethasone Compared to the Usual Treatment of Cyclophosphamide, Bortezomib, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients With Kidney Failure
- Conditions
- Myeloma Multiple
- Interventions
- Registration Number
- NCT07085728
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
This study is being done to answer the following question:
Can the addition of daratumumab-hyaluronidase to the usual treatment of bortezomib and dexamethasone improve kidney function in patients who are newly diagnosed with multiple myeloma and have kidney failure? This study is being done because the investigators want to find out if this approach is better or worse than the usual approach for the participant's newly diagnosed multiple myeloma. The usual approach is defined as care most people get for multiple myeloma.
If the participant decides to take part in this study, they will either get the study medications daratumumab-hyaluronidase, bortezomib, and dexamethasone for four months (4 cycles), or the typical medications used to treat your cancer (cyclophosphamide, bortezomib, and dexamethasone) for 4 months (4 cycles).
After the participant finishes their study treatment, their doctor will continue to follow their condition for 10 years to watch them for side effects and monitor their disease status. Their doctor will follow up with them every 3 months for years 1 and 2 and then every 6 months for years 3 through 10.
- Detailed Description
2.1 Primary Objectives 2.1.1 To determine whether incorporation of daratumumab-hyaluronidase into the treatment algorithm for newly diagnosed light chain cast nephropathy (LCCN) will improve efficacy measured by renal response rates (RRR) per International Myeloma Working Group (IMWG) renal response criteria over 4 cycles of treatment.
2.2 Secondary Objectives 2.2.1 To evaluate the safety profile of daratumumab-hyaluronidase replacing cyclophosphamide in combination with bortezomib and dexamethasone and to compare treatment-related grades 3-5 adverse event rates based on CTCAE criteria 2.2.2 To evaluate the myeloma response per IMWG uniform response criteria over 4 cycles of therapy 2.2.3 To evaluate progression-free and overall survival
2.3 Exploratory Objectives 2.3.1 To characterize renal function over time 2.3.2 To assess stem cell mobilization initiation and collection yield in patients eligible for autologous stem cell transplant (ASCT) who undergo mobilization 2.3.3 To assess rate of eligible patients undergoing ASCT 2.3.4 To assess treatment exposure and adherence 2.3.5 To assess the association of renal impairment stage at baseline and renal response with survival outcomes
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 74
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ARM A (Cy-Bor-Dex) Cyclophosphamide Cyclophosphamide-Bortezomib-Dexamethasone (4 cycles) ARM A (Cy-Bor-Dex) Bortezomib (VELCADE) Cyclophosphamide-Bortezomib-Dexamethasone (4 cycles) ARM A (Cy-Bor-Dex) Dexamethasone Cyclophosphamide-Bortezomib-Dexamethasone (4 cycles) ARM B (Dara-Bor-Dex) Bortezomib (VELCADE) Daratumumab-Bortezomib-Dexamethasone ARM B (Dara-Bor-Dex) Dexamethasone Daratumumab-Bortezomib-Dexamethasone ARM B (Dara-Bor-Dex) Daratumumab-hyaluronidase Daratumumab-Bortezomib-Dexamethasone
- Primary Outcome Measures
Name Time Method Renal Response Rate Assessed every cycle on treatment up to 4 cycles (cycle duration=28 days) Renal response rate (RRR) is the proportion of patients achieving complete or partial renal response based on International Myeloma Working Group (IMWG) renal response criteria (Dimopoulos 2023) over 4 cycles of treatment.
- Secondary Outcome Measures
Name Time Method Grade 3-5 Overall Toxicity Rate Assessed every cycle on treatment up to 4 cycles (cycle duration=28 days) Grade 3-5 overall toxicity rate is the proportion of participants who experience a maximum grade 3-5 treatment-related adverse event (AE) based on the Common Toxicity Criteria for Adverse Events Version 5.0 (CTCAEv5).
Grade 3-5 Non-Hematologic Toxicity Rate Assessed every cycle on treatment up to 4 cycles (cycle duration=28 days) Grade 3-5 non-hematologic toxicity rate is the proportion of participants who experience a maximum grade 3-5 treatment-related non-hematologic AE based on CTCAEv5.
Grade 3-5 Hematologic Toxicity Rate Assessed every cycle on treatment up to 4 cycles (cycle duration=28 days) Grade 3-5 hematologic toxicity rate is the proportion of participants who experience a maximum grade 3-5 treatment-related hematologic AE based on CTCAEv5.
Best Response Assessed every cycle on treatment up to 4 cycles (cycle duration=28 days) Best response is the frequency of participants achieving stringent complete response (sCR), complete response (CR), partial response (PR), stable disease (SD) or disease progression (PD) based on International Myeloma Working Group (IMWG) uniform response criteria (URC; Durie 2006) over 4 cycles of treatment.
Progression-Free Survival Disease assessed every cycle on treatment (cycle duration=28 days) and in long-term follow-up every 3 months for years 1-2 and every 6 months years 3-10 Progression-free survival (PFS) based on the Kaplan-Meier method defined as the time from randomization until the earlier of progression (PD per IMWG URC) or death due to any cause; Patients alive without disease progression will be censored at date of last disease evaluation; Only deaths that occur within 3 months of the last disease evaluation are considered events.
Overall Survival Assessed up to 10 years from study entry Overall survival (OS) based on the Kaplan-Meier method is defined as the duration of time from treatment start to date of death or censored at the date last known alive.