CARO: 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

Sponsor
iOMEDICO AG (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02970747
Collaborator
Amgen (Industry)
409
1
104.1
3.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
409 participants
Observational Model:
Case-Only
Time Perspective:
Prospective
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
Actual Study Start Date :
Oct 25, 2016
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Car/Len/Dex (KRd)

Patients treated with carfilzomib, lenalidomide and dexamethasone dosage form, dosage, frequency and duration of treatment according to current SmPC

Drug: Carfilzomib
In accordance with SmPC.
Other Names:
  • Kyprolis®
  • Car/Dex (Kd)

    Patients treated with carfilzomib and dexamethasone dosage form, dosage, frequency and duration of treatment according to current SmPC

    Drug: Carfilzomib
    In accordance with SmPC.
    Other Names:
  • Kyprolis®
  • Car/Dex/Dara (KdD)

    Patients treated with carfilzomib, dexamethasone and daratumumab dosage form, dosage, frequency and duration of treatment according to current SmPC

    Drug: Carfilzomib
    In accordance with SmPC.
    Other Names:
  • Kyprolis®
  • Outcome Measures

    Primary Outcome Measures

    1. Patients' adherence and persistence to carfilzomib therapy [Duration of Carfilzomib therapy, up to 24 months after last patient in]

      Patients' adherence and persistence to carfilzomib therapy

    Secondary Outcome Measures

    1. Patients' adherence and persistence to lenalidomide, dexamethasone and daratumumab therapy [Duration of Carfilzomib therapy, up to 24 months after last patient in]

      Patients' adherence and persistence to lenalidomide, dexamethasone and daratumumab therapy

    Other Outcome Measures

    1. Median Progression-free Survival (PFS) [up to 24 months after last patient in]

      Median Progression-free Survival (PFS)

    2. Overall Survival (OS) rate at 24 months [24 months]

      Overall Survival (OS) rate at 24 months

    3. Median Time to Response (TTR) [up to 24 months after last patient in]

      Median Time to Response (TTR)

    4. Median Duration of Response (DOR) [up to 24 months after last patient in]

      Median Duration of Response (DOR)

    5. Overall Response Rate (ORR) [up to 24 months after last patient in]

      ORR is defined as ≥ Very Good Partial Response (VGPR) + Partial Response (PR)

    6. 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 [Duration of Carfilzomib therapy (+ 30 days), up to 25 months after last patient in]

      AE, SAE and ADR are documented in the eCRF and will be used for safety assessment.

    7. To assess health-related QoL using the validated BOMET-QoL-10 questionnaire [Baseline, 6, 12, 18, 24, End of Treatment (latest up to 24 months after last patient in)]

      QoL data will be collected at baseline, after 6, 12, 18, 24 months (during treatment) and at the end of Carfilzomib therapy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centrum für Hämatologie und Onkologie Bethanien Frankfurt Germany 60389

    Sponsors and Collaborators

    • iOMEDICO AG
    • Amgen

    Investigators

    • Principal Investigator: Wolfgang Knauf, Professor, Centrum für Hämatologie und Onkologie Bethanien, Germany, 60389 Frankfurt a.M.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    iOMEDICO AG
    ClinicalTrials.gov Identifier:
    NCT02970747
    Other Study ID Numbers:
    • IOM-070337
    First Posted:
    Nov 22, 2016
    Last Update Posted:
    Jun 6, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 6, 2022