Real-world Use of Carfilzomib Among Multiple Myeloma Patients in Europe

Real-world Use of Carfilzomib Among Multiple Myeloma Patients in Europe Who Have Received at Least One Prior Therapy.

With the recent addition of carfilzomib as a treatment option for multiple myeloma, no data is available yet on how the drug is being used outside of the clinical trial setting.

This study will therefore provide essential data to demonstrate the real world utilization of carfilzomib in routine clinical practice, including dosage, administration schedule, regimen, duration of treatment and reason for discontinuation in Europe.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma

Detailed Description

With the recent addition of carfilzomib as a treatment option for multiple myeloma, no data is available yet on how the drug is being used outside of the clinical trial setting.

The Primary Objective is to describe carfilzomib utilisation in routine clinical practice, including dosage, administration schedule, regimen, duration of treatment and reason for discontinuation.

• Secondary Objectives:
• Describe the population treated with carfilzomib in terms of demographics, multiple myeloma (MM) disease characteristics, treatment history, and comorbidities.
• Describe the safety profile of carfilzomib in routine clinical practice.
• Describe response to treatment as assessed by the physician and recorded in the medical file.
• Describe healthcare resource utilisation of subjects treated with carfilzomib, in terms of unplanned hospitalisations.
• Describe the reasons for choosing carfilzomib as the MM treatment of choice.
• Describe specific concomitant therapy (bisphosphonates, thromboprophylaxis, antihypertensive treatment, anti-infective treatment) and whether these therapies were used as prophylaxis or as treatment.
• Describe a cardiovascular assessment at carfilzomib regimen initiation and at occurrence of cardiac adverse events, where available per routine care (electrocardiogram [ECG], echocardiography, left ventricular ejection fraction).

• Study Type: Observational
• Enrollment (Actual): 705

Contacts and Locations

Study Locations

• Austria
  • Braunau, Austria, 5280
    • Krankenhaus Sankt Josef Braunau
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Leoben, Austria, 8700
    • Landeskrankenhaus Hochsteiermark
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Rankweil, Austria, 6830
    • Landeskrankenhaus Rankweil
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
  • Schwarzach im Pongau, Austria, 5620
    • Kardinal Schwarzenbergsches Krankenhaus
  • Steyr, Austria, 4400
    • Landeskrankenhaus Steyr
  • Waidhofen an der Ybbs, Austria, 3340
    • Landesklinikum Waidhofen an der Ybbs
  • Wels, Austria, 4600
    • Klinikum Wels - Grieskirchen GmbH
  • Wien, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
  • Wiener Neustadt, Austria, 2700
    • Krankenhaus Wiener Neustadt
• Belgium
  • Bonheiden, Belgium, 2820
    • Imelda Ziekenhuis vzw
  • Brussels, Belgium, 1160
    • Hopital Delta
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Geel, Belgium, 2440
    • Algemeen Ziekenhuis Sint-Dimpna
  • Gent, Belgium, 9000
    • Algemeen Ziekenhuis Sint Lucas
  • Haine Saint Paul - La Louviere, Belgium, 7100
    • Centres Hospitaliers Jolimont - Hopital de Jolimont
  • Ieper, Belgium, 8900
    • JAN YPERMAN Ziekenhuis
  • Liege, Belgium, 4000
    • Centre Hospitalier Regional de la Citadelle
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege - Sart Tilman
  • Sint-Niklaas, Belgium, 9100
    • Algemeen Ziekenhuis Nikolaas Campus Sint-Niklaas
  • Tournai, Belgium, 7500
    • Centre Hospitalier Wallonie picarde - Site IMC
  • Verviers, Belgium, 4800
    • Centre Hospitalier Regional Verviers
• Bulgaria
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment of Hematology Diseases EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Alexandrovska
  • Sofia, Bulgaria, 1606
    • Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni nemocnice Olomouc
  • Plzen, Czechia, 304 60
    • Fakultni nemocnice Plzen
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• France
  • Amiens Cedex 1, France, 80054
    • Centre Hospitalier René Dubos
  • Avignon Cedex 9, France, 84902
    • Centre Hospitalier Henri Duffaut
  • Bayonne, France, 64109
    • Centre Hospitalier de la Cote Basque
  • Creteil, France, 94010
    • Hôpital Henri Mondor
  • Grenoble Cedex 9, France, 38043
    • Centre Hospitalier Universitaire de Grenoble
  • Limoges Cedex, France, 87042
    • Centre Hospitalier Regional Universitaire de Limoges - Hopital Dupuytren
  • Montpellier cedex 5, France, 34295
    • Centre Hospitalier Universitaire de Montpellier - Hopital Saint Eloi
  • Nimes cedex 09, France, 30029
    • Groupe Hospitalo Universitaire de Nimes - Hopital Caremeau
  • Paris, France, 75013
    • Hopital Pitie-Salpetriere
  • Paris, France, 75015
    • Groupe Hospitalier Necker - Enfants Malades
  • Paris, France, 75014
    • Hôpital Cochin
  • Poitiers Cedex, France, 86021
    • Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
  • Reims Cedex, France, 51056
    • Centre Hospitalier Universitaire de Reims - Hôpital Robert Debré
  • Saint Quentin, France, 02321
    • Centre Hospitalier de Saint Quentin
  • Strasbourg, France, 67000
    • Clinique Sainte Anne
• Greece
  • Alexandroupoli, Greece, 68100
    • University General Hospital of Evros-Alexandroupolis District
  • Athens, Greece, 11527
    • General Hospital of Athens Laiko
  • Athens, Greece, 18547
    • Metropolitan Hospital
  • Athens, Greece, 10676
    • General Hospital Evangelismos
  • Athens, Greece, 11526
    • Errikos Dunant Hospital Center
  • Athens, Greece, 11527
    • General Hospital of Athens Georgios Gennimatas
  • Athens, Greece, 11527
    • Laikon University Hospital
  • Athens, Greece, 11528
    • University of Athens School of Medicine Alexandra Hospital
  • Athens, Greece, 12462
    • University General Hospital Attikon
  • Athens, Greece, 15562
    • Metropolitan General
  • Heraklion, Greece, 71110
    • University Hospital of Heraklion
  • Larissa, Greece, 41110
    • University Hospital of Larissa
  • Patra, Greece, 26504
    • General University Hospital of Patras Panagia i Voithia
  • Patra, Greece, 26335
    • General Hospital of Patras Agios Andreas
  • Piraeus, Greece, 18537
    • Special Anticancer Hospital of Piraeus Metaxa
  • Thessaloniki, Greece, 54007
    • Theagenion Cancer Hospital of Thessaloniki
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki Georgios Papanikolaou
• Israel
  • Petah Tiqva, Israel, 4941492
    • Rabin Medical Center - Beilinson Hospital
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Alessandria, Italy, 15121
    • Azienda ospedaliera Santi Antonio e Biagio e Cesare Arrigo
  • Bagno A Ripoli (FI), Italy, 50012
    • Azienda Unita Sanitaria Locale Toscana Centro
  • Barletta, Italy, 76121
    • Ospedale Monsignor Raffaele Dimiccoli
  • Benevento, Italy, 82100
    • Azienda Ospedaliera G Rummo
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
  • Brindisi, Italy, 72100
    • Presidio Ospedaliero Di Summa Perrino
  • Cagliari, Italy, 09121
    • Azienda Ospedaliera Brotzu Presidio Ospedaliero A Businco Centro di Riferimento Oncologico Regionale
  • Cuneo, Italy, 12100
    • Azienda Ospedaliera Santa Croce E Carle
  • Lecco, Italy, 23900
    • Azienda Ospedaliera di Alessandro Manzoni Lecco
  • Livorno, Italy, 57123
    • Spedali Riuniti di Livorno
  • Messina, Italy, 98158
    • Azienda Ospedaliera Papardo
  • Milano, Italy, 20141
    • Irccs Istituto Europeo Di Oncologia
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Pagani (SA), Italy, 84016
    • Presidio Ospedaliero Andrea Tortora
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
  • Perugia, Italy, 06156
    • Azienda Ospedaliera di Perugia Ospedale Santa Maria della Misericordia
  • Pescara, Italy, 65124
    • Ospedale Civile Spirito Santo
  • Potenza, Italy, 85100
    • Azienda Ospedaliera San Carlo
  • Reggio Calabria, Italy, 89124
    • Grande Ospedale Metropolitano Bianchi Melacrino Morelli
  • Reggio Emilia, Italy, 42100
    • Azienda Unita Sanitaria Locale Istituto di Ricovero di Reggio Emilia Arcispedale Santa Maria Nuova
  • Roma, Italy, 00133
    • Fondazione Policlinico Tor Vergata
  • Roma, Italy, 00144
    • Ospedale Sant Eugenio
  • Roma, Italy, 00161
    • Azienda Ospedaliera Policlinico Umberto I
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant Andrea
  • Salerno, Italy, 84131
    • Azienda Ospedaliera Universitaria Ospedale San Giovanni di Dio e Ruggi D Aragona
  • Taranto, Italy, 74123
    • Presidio Ospedaliero San Giuseppe Moscati
  • Torino, Italy, 10126
    • Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria Integrata di Udine
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata di Verona Ospedale G B Rossi Borgo Roma
• Netherlands
  • Beverwijk, Netherlands, 1942 LE
    • Rode Kruis Ziekenhuis
  • Breda, Netherlands, 4819 EV
    • Amphia ziekenhuis, locatie langendijk
  • Den Haag, Netherlands, 2545 CH
    • Hagaziekenhuis, locatie Leyweg
  • Nieuwegein, Netherlands, 3435 CM
    • Sint Antonius Ziekenhuis, locatie Nieuwegein
  • Schiedam, Netherlands, 3118 JH
    • Franciscus Vlietland
  • Venlo, Netherlands, 5912 BL
    • Viecuri Medisch Centrum
• Norway
  • Oslo, Norway, 0372
    • Oslo Universitetssykehus HF
• Romania
  • Baia Mare, Romania, 430031
    • Spitalul Judetean de Urgenta Dr Constantin Opris Baia Mare
  • Brasov, Romania, 500152
    • Policlinica de Diagnostic Rapid
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute
  • Bucharest, Romania, 020125
    • Spitalul Clinic Colentina
  • Bucharest, Romania, 030171
    • Coltea Clinical Hospital
  • Bucuresti, Romania, 010825
    • Spitalul Universitar de Urgenta Militar Central "Dr. Carola Davila"
  • Bucuresti, Romania, 022328
    • Fundeni Clinical Institute
  • Cluj-Napoca, Romania, 400124
    • Profesor Dr Ion Chiricuta Institut of Oncology
  • Craiova, Romania, 200143
    • Spitalul Clinic Municipal Filantropia Craiova
  • Iasi, Romania, 700483
    • Iasi Regional Oncology Institute
  • Oradea, Romania, 410469
    • Spitalul Clinic Dr Gavril Curteanu Oradea
  • Targu Mures, Romania, 540136
    • Targu-Mures County Emergency Clinical Hospital
  • Timisoara, Romania, 300239
    • SC Oncomed SRL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Multiple Myeloma

Description

Inclusion Criteria:

• Age 18 years or older at the time of carfilzomib initiation
• At least one prior line of MM treatment has been received
• Carfilzomib treatment has been initiated per routine practice and is currently ongoing
• At least one administration of carfilzomib in a combination regimen (ie, not monotherapy) has been received
• Provided written informed consent prior to abstraction of any data, in countries where written informed consent is required.
• Subjects who previously completed treatment with carfilzomib in a clinical trial, a compassionate use program or through routine practice, are eligible to take part in the study.
• Subjects who receive radiotherapy concurrently with carfilzomib treatment are also eligible to take part in the study.
• Subjects who initiate carfilzomib treatment on a combination regimen, subsequently discontinue all concomitant medications but remain on carfilzomib monotherapy in later cycles, remain eligible for participation in the study.
• Subjects who are also enrolled in other observational studies in which standard of care is not altered are eligible to take part in the study,

Exclusion Criteria:

• Subjects who are enrolled in a carfilzomib clinical trial will not be eligible to additionally take part in this observational study.
• Subjects who are receiving carfilzomib treatment within a compassionate use program will not be eligible to take part in this observational study. If a subject who has enrolled into this observational study, also enrolls in a clinical trial in which MM treatment and/or disease management is protocol-specified, the subject becomes ineligible and the subject's data will be censored from the time the subject enrolled the clinical trial.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carfilzomib starting dose	Carfilzomib dose at first administration	18 months
Carfilzomib dose	Carfilzomib dose at subsequent administrations	18 months
Carfilzomib dose modification	Modification includes change in dose level, dose interruption, and dose delays	18 months
Time to carfilzomib dose modification	At least one carfilzomib dose modification, escalation or reduction	18 months
Reason for dose modification	Reason for dose modification or delay	18 months
Number of cycles started	Number of carfilzomib treatment cycles started throughout study period	18 months
Carfilzomib regimen	Treatment combination	18 months
Carfilzomib dosing frequency	Number of administrations per cycle	18 months
Carfilzomib dosing schedule	Timing of carfilzomib administration within treatment cycle	18 months
Carfilzomib duration of treatment	Duration of carfilzomib treatment	18 months
Starting dose of concomitant anti-myeloma agents	Dose of combination agents (e.g. lenalidomide or dexamethasone) at baseline	18 months
Dose modification for concomitant anti-myeloma agents	Modification includes change in dose level, dose interruption, and dose delays	18 months
Reason for frequency modification	At least 1 change in frequency of carfilzomib administration.	18 months
Reason for change in frequency of concomitant multiple myeloma therapies	Reason for change in frequency of administration.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Staging System (ISS) score and revised ISS stage at diagnosis and carfilzomib regimen initation	International Staging System (ISS) score of I, II, III, or unkown	18 months
Eastern Cooperative Oncology Group (ECOG) performance status	ECOG performance status category at multiple myeloma diagnosis and carfilzomib regimen initiation.	18 months
Cytogenetic risk profile at diagnosis	Cytogenetic risk profile at diagnosis	18 months
Presence of CRAB features (i.e. hypercalcemia, renal insufficiency, anemia and/or bone pain)	Presence of CRAB features at MM diagnosis	18 months
Presence of comorbidities	Diagnosed at any point in time before carflzomib regimen initiation	18 months
Previously received anti-myeloma treatment	Treatment history	18 months
Response to prior treatment	Response to prior treatment received before initiation of carfilzomib	18 months
Number of prior relapses	Type of relapse (molecular, hematologic, or symptomatic)	18 months
Adverse event	All grade 3 or above adverse events.	18 months
Time to adverse event	All grade 3 or above adverse events	18 months
Electrocardiogram (ECG) changes	ECG changes as recorded in tests performed per routine practice	18 months
Decrease in left ventricular ejection fraction (LVEF)	LVEF decrease as recorded in tests performed per routine practice	18 months
Initiation or dose increase of antihypertensive treatment	Initiation or dose increase of existing antihypertensive treatment	18 months
Initiation or dose increase of existing heart failure treatment	Initiation or dose increase of existing heart failure treatment	18 months
Response to carfilzomib treatment	Physician-assessed response as recorded on the medical charts	18 months
Type of relapse	Molecular, hematologic or symptomatic relapse	18 months
Number of unplanned hospitalisations	Initiation or dose increase of existing heart failure treatment	18 months
Concomitant therapy not part of the carfilzomib regimen	Concomitant therapy not part of the carfilzomib regimen	18 months
Planned subsequent treatment regimen	Planned subsequent treatment regimen catergory	18 months
Patient age	Patient age	18 months
Patient sex	Patient sex	18 months
Patient height	Patient height	18 months
Patient weight	Patient weight	18 months
MRI (magnetic resonance imaging) performed at MM diagnosis and carfilzomib regimen initiation.	MRI (magnetic resonance imaging)	18 months
PET-CT (positron emission tomography-computed tomography) performed at MM diagnosis and carfilzomib regimen initiation.	PET-CT (positron emission tomography-computed tomography)	18 months
Measurement of Serum M component at MM diagnosis and carfilzomib regimen initiation.	Serum M component	18 months
Measurement of Urine M component at MM diagnosis and carfilzomib regimen initiation.	Urine M component	18 months
Measurement of serum albumin at MM diagnosis and carfilzomib regimen initiation.	Serum albumin	18 months
Measurement of serum beta-2-microglobulin at MM diagnosis and carfilzomib regimen initiation.	Beta-2-microglobulin	18 months
Measurement of percent of plasma cells in bone marrow at MM diagnosis and carfilzomib regimen initiation.	Percent of plasma cells in bone marrow	18 months
Baseline measurement of lactate dehydrogenase at MM diagnosis and carfilzomib regimen initiation.	Lactate dehydrogenase	18 months
ECG (electrocardiogram)	ECG (electrocardiogram)	18 months
Echocardiogram	Echocardiogram	18 months
LVEF (left ventricular ejection fraction) assessment	LVEF (left ventricular ejection fraction) assessment	18 months
Computed Tomography (CT) performed at MM diagnosis and carfilzomib regiment initiation.	Computed tomography	18 Months
Myeloma/Osteolytic lesions detected by MRI, PET-CT, and X-ray at MM diagnosis and carfilzomib regimen initiation	Myeloma/Osteolytic lesions detected by MRI, PET-CT, and X-ray at MM diagnosis and carfilzomib regimen initiation	18 months

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Leleu, X, Katodritou, E, Kuehr, T, Terpos, E, Caers, J, Zambello, R, et al. Real-world use of carfilzomib combined with lenalidomide and dexamethasone in patients with multiple myeloma in Europe and Israel. eJHaem. 2022; 1- 10. 10.1002/jha2.595
• Terpos E, Zambello R, Leleu X, Kuehr T, Badelita SN, Katodritou E, Brescianini A, Liang T, Wetten S, Caers J. Real-World Use and Effectiveness of Carfilzomib Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma in Europe. Cancers (Basel). 2022 Oct 28;14(21):5311. doi: 10.3390/cancers14215311.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Actual): March 17, 2020
• Study Completion (Actual): March 17, 2020

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 20150262

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No