Multiple myeloma MedDRA version: 19.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Kyprolis
Product Name: Kyprolis
Product Code: PR-171
Pharmaceutical Form: Powder for solution for injection
INN or Proposed
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease-related 1. Symptomatic multiple myeloma 2. Measurable disease, as defined by one or more of the following (assessed within 21 days prior to randomization): - Serum M-protein = 0.5 g/dL - Urine Bence-Jones protein = 200 mg/24 hours - For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) = 750 mg/dL (0.75 g/dL) 3. Prior treatment with at least one, but no more than three, regimens for multiple myeloma 4. Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent line of therapy are eligible) 5. Achieved a response to at least one prior regimen (defined as = 25% decrease in M protein [or total protein in countries in which electrophoresis is not routinely available]) Demographic 6. Age = 18 years 7. Life expectancy = 3 months 8. Eastern Cooperative Oncology Group (ECOG) performance status 0–2 Laboratory 9. Adequate hepatic function, with serum ALT = 3.5 times the upper limit of normal and serum direct bilirubin = 2 mg/dL (34 µmol/L) within 21 days prior to randomization 10. Absolute neutrophil count (ANC) = 1.0 × 10^9/L within 21 days prior to randomization 11. Hemoglobin = 8 g/dL (80 g/L) within 21 days prior to randomization (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines) 12. Platelet count = 50 × 10^9/L (= 30 × 10^9/L if myeloma involvement in the bone marrow is > 50%) within 21 days prior to randomization 13. Creatinine clearance (CrCl) = 50 mL/minute (either measured or calculated using a standard formula such as Cockcroft and Gault) within 21 days prior to randomization Ethical/Other 14. Written informed consent in accordance with federal, local, and institutional guidelines. 15. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception according to, and for the timeframe outlined in the RevAssist program (US participants), RevAid program (Canadian participants) or Appendix F (all other participants) 16. Male subjects must agree to practice contraception according to, and for the timeframe outlined in the RevAssist program (US participants), RevAid program (Canadian participants) or Appendix F (all other participants) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 421 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 359
Exclusion criteria
Exclusion criteria: Disease-related 1. If previously treated with bortezomib (alone or in combination), progression during treatment 2. If previously treated with a lenalidomide and dexamethasone (len/dex) combination: - Progression during the first 3 months of initiating treatment - Any progression during treatment if the lenalidomide/dexamethasone combination was the subject's most recent line of therapy 3. Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded 4. Prior carfilzomib treatment 5. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 6. Waldenström's macroglobulinemia or IgM myeloma 7. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential) Concurrent Treatments 8. Chemotherapy or investigational agent within 3 weeks prior to randomization or antibody therapy within 6 weeks prior to randomization 9. Radiotherapy to multiple sites or immunotherapy/antibody therapy within 28 days prior to randomization; localized radiotherapy to a single site within 7 days prior to randomization 10. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 21 days prior to randomization Concurrent Conditions 11. Pregnant or lactating females 12. Major surgery within 21 days prior to randomization 13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization 14. Known human immunodeficiency virus infection 15. Active hepatitis B or C infection 16. Myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker 17. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization 18. Other malignancy, including myelodysplastic syndrome (MDS), within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Score 6 or less with stable prostate specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas 19. Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to randomization 20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) 21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment 22. Ongoing gra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare PFS in subjects with relapsed multiple myeloma who are receiving CRd versus PFS in subjects receiving Rd alone in a randomized multicenter setting.; Secondary Objective: Secondary objectives include investigating the effect of carfilzomib given with lenalidomide and dexamethasone on other standard efficacy variables including overall survival (OS), overall response rate (ORR [sCR + CR + VGPR + PR]), disease control rate (DCR [overall responses + minimal response (MR ) + stable disease lasting at least 8 weeks]), duration of response (DOR), change in the Global Health Status Scale of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Module (QLQ-C30), time to progression (exploratory), all other QOL domain subscales in EORTC QLQ-C30 and QLQ-MY20 (exploratory), time to next treatment (exploratory), and clinical benefit response (CBR = [ORR + MR1], exploratory). Additionally, this study will examine the safety profile of CRd compared with Rd alone based on the incidence and severity of AEs and laboratory changes. ;Primary end point(s): Progression free survival (PFS);Timepoint(s) of evaluation of this end point: Progression free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Duration of response (DOR) • Change in the Global Health Status Scale of the EORTC Quality of Life Core Module (QLQ-C30) •Safety ;Timepoint(s) of evaluation of this end point: All the secondary endpoints will be evaluated at the same time as the primary endpoint, progression free survival, except for overall survival. For overall survival, the final analysis will be performed after approximately 510 deaths have occurred, which is anticipated to be approximately 72 months after the first subject is randomized. | — |
Countries
Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Poland, Russian Federation, Spain, Sweden, Ukraine, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed