Clinical trial NCT02970747: Non-interventional Study of Kyprolis® in Combination With Revlimid® and Dexamethasone or Dexamethasone Alone or in Combination With Darzalex® and Dexamethasone in Multiple Myeloma Patients
Official title: A Non-interventional Study of Carfilzomib (Kyprolis®) in Combination With Lenalidomide (Revlimid®) and Dexamethasone or Carfilzomib in Combination With Dexamethasone Alone or Carfilzomib in Combination With Daratumumab (Darzalex®) and Dexamethasone in Patients With Multiple Myeloma Who Have Received at Least One Prior Therapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Multiple Myeloma in Relapse
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2016-11-22
Enrollment: 359
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with multiple myeloma (MM) who have received at least one prior therapy

Brief summary: The objective of this non-interventional study (NIS) is to evaluate patients' adherence and persistence to carfilzomib therapy in combination with lenalidomide and dexamethasone or in combination with dexamethasone alone or in combination with daratumumab and dexamethasone in adult patients with multiple myeloma (MM) who have received at least one prior therapy in a real-life setting.

Detailed description: The dual combination of lenalidomide (Revlimid®) (R) and dexamethasone (d) (Rd) as well as the dual combination of bortezomib (Velcade®, V) and dexamethasone (Vd) are standard regimens 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 or refractory MM (RRMM).1 Three pivotal trials were conducted leading to market authorization of carfilzomib in combination with lenalidomide and dexamethasone or in combination with dexamethasone alone or in combination with dexamethasone and daratumumab for the treatment of MM patients who have received at least one prior therapy.

ASPIRE, NCT010803912 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 relapsed MM (RMM). 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.

ENDEAVOR, NCT015688663 To compare the efficacy and safety of the dual combination therapy Kd with the dual combination therapy Vd, a randomized, multicenter, open-label phase III study was performed in patients with RRMM. 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 RRMM.

CANDOR, NCT031586884-7 To compare the efficacy and safety of carfilzomib in combination with dexamethasone and daratumumab (KdD) with the dual combination therapy Kd, a randomized, multicenter, open-label phase III study was performed in patients with RRMM. Patients in both arms received treatment until progression. The trial met its primary endpoint PFS (HR for progression or death, 0.59). Median PFS was 28.6 months in the KdD arm and 15.2 months with Kd treatment with a median follow-up time of 27.8 months and 27.0 months, respectively. Further, KdD treatment demonstrates improved response rates by providing deeper responses. ORR was 84% (with 29% complete response (CR) or better) for KdD treatment and 75% (with 10% CR or better) for Kd treatment (p=0.0080). The minimal residual disease (MRD) negative CR rate at 12 months is nearly 10-times higher with KdD (12.5%) compared to Kd (1.3%). Overall, the safety profile is consistent with the known safety profiles of each agent, with the exception of an imbalance in treatment-emergent fatal AEs, which might be partially explained by longer treatment exposure, age, and frailty status.

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,the Kd and the KdD regimen have been systematically collected and analyzed. Thus, after market approval of KRd, Kd and KdD 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 both regimens in a real-life setting.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older.
* Patients with MM who have received at least one prior therapy.
* Indication for treatment as assessed by the treating physician.
* Decision for second- or subsequent-line treatment with the combination therapy carfilzomib/ lenalidomide/ dexamethasone or carfilzomib/ dexamethasone or carfilzomib/ dexamethasone/ daratumumab
* Signed written informed consent.
* Criteria according to the current Summary of Product Characteristics (SmPC) for Kyprolis® (Carfilzomib)

Exclusion Criteria:

* Contraindications according to the current SmPC for Kyprolis® (Carfilzomib)

Primary outcomes:
measure: Patients' adherence and persistence to carfilzomib therapy
timeFrame: Duration of Carfilzomib therapy, up to 24 months after last patient in
Secondary outcomes:
measure: Patients' adherence and persistence to lenalidomide, dexamethasone and daratumumab therapy
timeFrame: Duration of Carfilzomib therapy, up to 24 months after last patient in
Other outcomes:
measure: Median Progression-free Survival (PFS)
timeFrame: up to 24 months after last patient in
measure: Overall Survival (OS) rate at 24 months
timeFrame: 24 months
measure: Median Time to Response (TTR)
timeFrame: up to 24 months after last patient in
measure: Median Duration of Response (DOR)
timeFrame: up to 24 months after last patient in
measure: Overall Response Rate (ORR)
timeFrame: up to 24 months after last patient in
measure: 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
timeFrame: Duration of Carfilzomib therapy (+ 30 days), up to 25 months after last patient in
measure: To assess health-related QoL using the validated BOMET-QoL-10 questionnaire
timeFrame: Baseline, 6, 12, 18, 24, End of Treatment (latest up to 24 months after last patient in)
Locations:
city: Frankfurt
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
Study officials:
affiliation: Centrum für Hämatologie und Onkologie Bethanien, Germany, 60389 Frankfurt a.M.
name: Wolfgang Knauf, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Engelhardt M, Ihorst G, Singh M, Rieth A, Saba G, Pellan M, Lebioda A. Real-World Evaluation of Health-Related Quality of Life in Patients With Multiple Myeloma From Germany. Clin Lymphoma Myeloma Leuk. 2021 Feb;21(2):e160-e175. doi: 10.1016/j.clml.2020.10.002. Epub 2020 Oct 24.