A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ARROW2)
Relapsed or Refractory Multiple Myeloma
About this trial
This is an interventional treatment trial for Relapsed or Refractory Multiple Myeloma focused on measuring Bone Marrow Cancer
Eligibility Criteria
Inclusion Criteria:
Multiple myeloma with documented relapse or progression after most recent myeloma treatment. Subjects refractory to the most recent line of therapy are eligible, unless last treatment contained proteasome inhibitor (PI) or lenalidomide and dexamethasone. Refractory is defined as disease that is nonresponsive or progresses within 60 days of last therapy.
Subjects must have at least PR to at least 1 line of prior therapy.
Subjects must have received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation maintenance therapy will be considered as 1 line of therapy).
Prior therapy with a PI or the combination of lenalidomide and dexamethasone are allowed if the patient had at least a PR to the most recent treatment with a PI or lenalidomide and dexamethasone, neither PI or lenalidomide and dexamethasone containing treatment were ceased due to toxicity, the patient has not relapsed within 60 days of discontinuation of the PI or lenalidomide and dexamethasone containing treatment. A history of prior neuropathy is permitted if this was not grade 3, grade 4 or grade 2 with pain and if not resolved within the 14 days before enrollment, is less than or equal to grade 2 without pain. Patients are permitted to have received single agent lenalidomide as maintenance therapy within 60 days of enrollment.
Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as long as the subject did not progress during the first 3 months after initiating lenalidomide and dexamethasone containing therapy.
Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:
- Immunoglobulin G (IgG) multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
- Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin E (IgE) multiple myeloma: serum M-protein level ≥ 0.5 g/dL
- Urine M-protein ≥ 200 mg per 24 hours
- In subjects without measurable serum or urine M-protein, serum-free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 ≤ 2
Other inclusion criteria may apply
Exclusion Criteria:
Waldenström macroglobulinemia.
Multiple myeloma of Immunoglobulin M (IgM) subtype.
Plasma cell leukemia (> 2.0 × 10^9 /L circulating plasma cells by standard differential).
Uncontrolled hypertension, defined as a subject whose blood pressure is greater than or equal to 160 mmHg systolic or greater than or equal to 100 mmHg diastolic when taken in accordance with the European Society of Hypertension/European Society of Cardiology 2018 guidelines (Section 12.10; Williams et al, 2018).
Active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.
Calculated or measured creatinine clearance < 30 mL/min (calculation must be based on the Cockcroft and Gault formula) within 28 days prior to randomization.
Other exclusion criteria may apply
Sites / Locations
- Robert A Moss Oncology
- Rocky Mountain Cancer Centers Denver Midtown
- Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut
- Baptist MD Anderson Cancer Center
- Advocate Lutheran General Hospital
- New York Oncology Hematology, PC
- Oncology Hematology Care Inc
- Texas Oncology-Denton
- US Oncology Research Investigational Products Center
- Oncology Consultants PA
- Texas Oncology
- United States Oncology Regulatory Affairs Corporate Office
- Universitaetsklinikum Salzburg
- University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
- University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
- Specialized Hospital for Active Treatment of Hematology Diseases EAD
- Fakultni nemocnice Brno
- Fakultni nemocnice Hradec Kralove
- Fakultni nemocnice Olomouc
- Vseobecna fakultni nemocnice v Praze
- Helsingin Yliopistollinen Keskussairaala
- Oulun Yliopistollinen Sairaala
- Turun Yliopistollinen Keskussairaala
- Centre Hospitalier Universitaire de Nantes
- Centre Hospitalier Universitaire Archet 2
- Hopital Saint Louis
- Hopital Pitie-Salpetriere
- Centre Hospitalier Lyon Sud
- Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie
- Centre Hospitalier Universitaire de Rennes
- Institut de Cancerologie Strasbourg
- Institut Universitaire du Cancer Toulouse Oncopole
- Centre Hospitalier Universitaire de Nancy - Hopital de Brabois
- Charité, Universitätsklinikum Berlin, Campus Benjamin Franklin
- Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
- Universitatsklinikum Hamburg-Eppendorf
- Universitatsklinikum Koln
- Johannes Gutenberg Universitaet Mainz
- University Hospital of Alexandroupolis
- General Hospital Evangelismos
- Agios Savvas Anticancer Hospital
- 251 General Airforce Hospital
- Alexandra Hospital
- Metropolitan Hospital
- General University Hospital of Patras Panagia i Voithia
- Theagenion Cancer Hospital of Thessaloniki
- General Hospital of Thessaloniki Georgios Papanikolaou
- Nagoya City University Hospital
- Toyohashi Municipal Hospital
- Tesshokai Kameda General Hospital
- National Hospital Organization Kyushu Cancer Center
- Ogaki Municipal Hospital
- National Hospital Organization Shibukawa Medical Center
- Japanese Red Cross Society Himeji Hospital
- Hyogo College of Medicine Hospital
- Hitachi Ltd Hitachi General Hospital
- University Hospital Kyoto Prefectural University of Medicine
- National Hospital Organization Sendai Medical Center
- Niigata Cancer Center Hospital
- National Hospital Organization Okayama Medical Center
- Japanese Red Cross Osaka Hospital
- Kindai University Hospital
- Osaka University Hospital
- Saitama Medical Center
- Tochigi Cancer Center
- Juntendo University Hospital
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research
- Japanese Red Cross Medical Center
- Hospital of Lithuanian University of Health Sciences Kaunas Clinics Public Institution
- Vilnius University Hospital Santaros Clinic Public Institution
- VU Medisch Centrum
- Gelre Ziekenhuizen
- Spaarne Gasthuis
- Fundeni Clinical Institute
- Institutul Clinic Fundeni
- Spitalul Clinic Coltea
- Spitalul Universitar de Urgenta Bucuresti
- Spitalul Clinic Colentina
- Institutul Oncologic Prof Dr Ion Chiricuta
- Institutul Regional de Oncologie Iasi
- Spitalul Clinic Dr Gavril Curteanu Oradea
- Spitalul Clinic Judetean de Urgenta Sibiu
- Spitalul Clinic Municipal de Urgenta Timisoara
- Regional Clinical Hospital
- Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department
- SBHI of Moscow city City clinical hospital na S P Botkin of Moscow city Healthcare department
- SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov
- Federal centre of heart, blood and endocrinology Almazova
- State Budget Educational Institution of High Professional Skills Samara State Medical University
- Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda
- Hospital Universitari Son Espases
- Hospital Clinico Universitario de Salamanca
- Hospital Universitari Germans Trias i Pujol
- Hospital Clinic i Provincial de Barcelona
- Hospital Universitario Quironsalud Madrid
- Clinica Universidad de Navarra
- Falu Lasarett
- Sahlgrenska Universitetssjukhuset
- Hallands Sjukhus Halmstad
- Sunderby Sjukhus
- Skanes Universitetssjukhus
- Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
- Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi
- Istanbul Universitesi Istanbul Tip Fakultesi
- Bagcilar Medipol Mega Universite Hastanesi
- Istanbul Florence Nightingale Hastanesi
- Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi
- Erciyes Universitesi Tip Fakultesi Mehmet Kemal Dedeman Hematoloji-Onkoloji Hastanesi
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Carfilzomib once-weekly
Carfilzomib twice-weekly
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2