Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Non-interventional Study of Kyprolis® in Combination With Revlimid® and Dexamethasone or Dexamethasone Alone in Multiple Myeloma Patients (CARO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02970747
Recruitment Status : Recruiting
First Posted : November 22, 2016
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
iOMEDICO AG

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 dexamethasone alone 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
Multiple Myeloma in Relapse Drug: Carfilzomib

Detailed Description:

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.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 300 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 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


Group/Cohort 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 Name: 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 Name: Kyprolis®




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. Median Progression-free Survival (PFS) [ Time Frame: 60 months ]
    Median Progression-free Survival (PFS)

  2. Overall Survival (OS) rate at 24 months [ Time Frame: 48 months ]
    Overall Survival (OS) rate at 24 months

  3. Median Time to Response (TTR) [ Time Frame: 60 months ]
    Median Time to Response (TTR)

  4. Median Duration of Response (DOR) [ Time Frame: 60 months ]
    Median Duration of Response (DOR)

  5. Overall Response Rate (ORR) [ Time Frame: 60 months ]
    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 [ Time Frame: 60 months ]
    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 [ 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adult patients with multiple myeloma (MM) who have received at least one prior therapy
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
  • 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)

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Beate Niemeier, Dr. + 49 761 15242 ext 13 beate.niemeier@iomedico.com

Locations
Layout table for location information
Germany
Centrum für Hämatologie und Onkologie Bethanien Recruiting
Frankfurt, Germany, 60389
Contact: Wolfgang Knauf, Professor         
Sponsors and Collaborators
iOMEDICO AG
Investigators
Layout table for investigator information
Principal Investigator: Wolfgang Knauf, Professor Centrum für Hämatologie und Onkologie Bethanien, Germany, 60389 Frankfurt a.M.

Layout table for additonal information
Responsible Party: iOMEDICO AG
ClinicalTrials.gov Identifier: NCT02970747     History of Changes
Other Study ID Numbers: IOM-070337
First Posted: November 22, 2016    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Lenalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors