Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02970747 |
| Other study ID # |
IOM-070337 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 25, 2016 |
| Est. completion date |
June 30, 2025 |
Study information
| Verified date |
July 2023 |
| Source |
iOMEDICO AG |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
