Non-interventional Study of Kyprolis® in Combination With Revlimid® and Dexamethasone or Dexamethasone Alone in Multiple Myeloma Patients (CARO)
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|ClinicalTrials.gov Identifier: NCT02970747|
Recruitment Status : Recruiting
First Posted : November 22, 2016
Last Update Posted : August 21, 2019
|Condition or disease||Intervention/treatment|
|Multiple Myeloma in Relapse||Drug: Carfilzomib|
The dual combination of lenalidomide (Revlimid®) (R) and dexamethasone (d) (Rd) is a standard regimen to treat MM patients who have received at least one prior therapy. Recently published clinical data indicate that the next-generation proteasome inhibitor carfilzomib (Kyprolis®) (K) may substantially change the treatment paradigm for patients with relapsed MM (RMM).
To compare the efficacy and safety of carfilzomib in combination with Rd (KRd) with the dual combination therapy Rd, a randomized, multicenter, open-label phase III study was performed in patients with RMM (ASPIRE, NCT01080391).2 After cycle 18, carfilzomib was discontinued in the KRd arm, but Rd administration was continued thereafter until disease progression. The trial met its primary endpoint progression-free survival (PFS) (Hazard Ratio (HR) for progression or death, 0.69; p=0.0001). Median PFS was 26.3 months with KRd treatment compared to 17.6 months with Rd treatment. The study further demonstrates that carfilzomib improves patients' overall survival (OS) rate at 24 months (KRd, 73.3% vs. Rd, 65.0%; HR for death, 0.79; p=0.04) and overall response rate (ORR) (KRd, 87.1% vs. Rd, 66.7%; p<0.001). Objective assessment of adverse events (AEs) and patient-reported outcomes (PRO) revealed that the benefit-risk ratio is favorable for the three-drug combination KRd.
To compare the efficacy and safety of carfilzomib in combination with dexamethasone (Kd) with the dual combination bortezomib and dexamethasone, a randomized, multicenter, open-label phase III study was performed in patients with RMM (ENDEAVOR, NCT01568866). Patients in both arms received treatment until progression. Results of the preplanned interim analysis show, that the trial met its primary endpoint PFS (HR for progression or death, 0.53; p<0.0001). Median PFS was 18.7 months with Kd treatment compared to 9.4 months with Vd treatment. In addition, the Kd combination therapy demonstrated superiority over the Vd combination therapy for secondary objectives, like ORR (77% vs. 63%; p<0.0001) and median duration of response (DOR) (21.3 months vs. 10.4 months). OS data were not available at time of analysis. Despite higher rates for cardiac and renal failure as well as higher incidence of hypertension and dyspnea in the Kd arm, carfilzomib given as a 30 min infusion has an acceptable safety profile, particularly with respect to lower peripheral neuropathy events. The number of patients who had ≥ grade 2 peripheral neuropathy was significantly higher in the Vd group than in the Kd group (32% vs. 6%). In conclusion, data of the ENDEAVOR study demonstrate, that carfilzomib given in combination with dexamethasone has a favorable benefit-risk profile and provides an important new treatment option for patients with relapsed/refractory MM (RRMM).
Up to now, no real-life data on patients' adherence, persistence, quality of life (QoL) and patterns of use, effectiveness and safety of the KRd and Kd regimen have been systematically collected and analyzed. Thus, after market approval of KRd and Kd as treatment for patients with MM who have received at least one prior therapy, the purpose of the CARO NIS is to evaluate patients' adherence, persistence and QoL as well as effectiveness and safety of the KRd regimen and the Kd regimen in a real-life setting.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|Official Title:||A Non-interventional Study of Carfilzomib (Kyprolis®) in Combination With Lenalidomide (Revlimid®) and Dexamethasone or Carfilzomib in Combination With Dexamethasone Alone in Patients With Multiple Myeloma Who Have Received at Least One Prior Therapy|
|Actual Study Start Date :||October 25, 2016|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||April 2022|
Patients treated with carfilzomib, lenalidomide and dexamethasone dosage form, dosage, frequency and duration of treatment according to current SmPC
In accordance with SmPC.
Other Name: Kyprolis®
Patients treated with carfilzomib and dexamethasone dosage form, dosage, frequency and duration of treatment according to current SmPC
In accordance with SmPC.
Other Name: Kyprolis®
- Patients' adherence and persistence to carfilzomib therapy [ Time Frame: Duration of Carfilzomib therapy, up to 36 months after last patient in ]Patients' adherence and persistence to carfilzomib therapy
- Patients' adherence and persistence to lenalidomide and dexamethasone therapy [ Time Frame: Duration of Carfilzomib therapy, up to 36 months after last patient in ]Patients' adherence and persistence to lenalidomide and dexamethasone therapy
- Median Progression-free Survival (PFS) [ Time Frame: 60 months ]Median Progression-free Survival (PFS)
- Overall Survival (OS) rate at 24 months [ Time Frame: 48 months ]Overall Survival (OS) rate at 24 months
- Median Time to Response (TTR) [ Time Frame: 60 months ]Median Time to Response (TTR)
- Median Duration of Response (DOR) [ Time Frame: 60 months ]Median Duration of Response (DOR)
- Overall Response Rate (ORR) [ Time Frame: 60 months ]ORR is defined as ≥ Very Good Partial Response (VGPR) + Partial Response (PR)
- To assess safety and tolerability measured by adverse events as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.03 [ Time Frame: 60 months ]AE, SAE and ADR are documented in the eCRF and will be used for safety assessment.
- To assess health-related QoL using the validated BOMET-QoL-10 questionnaire [ Time Frame: Baseline, 6, 12, 18, 24, 60 months ]QoL data will be collected at baseline, after 6, 12, 18, 24 months and at the end of Carfilzomib therapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02970747
|Contact: Beate Niemeier, Dr.||+ 49 761 15242 ext email@example.com|
|Centrum für Hämatologie und Onkologie Bethanien||Recruiting|
|Frankfurt, Germany, 60389|
|Contact: Wolfgang Knauf, Professor|
|Principal Investigator:||Wolfgang Knauf, Professor||Centrum für Hämatologie und Onkologie Bethanien, Germany, 60389 Frankfurt a.M.|