Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Kyprolis
Product Name: Carfilzomib
Product Code: PR-171
Pharmaceutical Form: Lyophilisate for solution for injection
INN or
506160 - CARFILZOMIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Sponsors
Onyx Therapeutics, Inc.; an Amgen Inc. subsidiary
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 101. Age = 18 years 102. Able to provide written informed consent in accordance with federal, local, and institutional guidelines 103. Relapsed multiple myeloma 104. Refractory multiple myeloma, defined as meeting 1 or more of the following: a. Nonresponsive to most recent therapy (stable disease or progressive disease [PD] while on treatment), or b. Disease progression within 60 days of discontinuation from most recent therapy 105. At least 2, but no more than 3, prior lines of therapy for multiple myeloma 106. Prior exposure to an IMiD 107. Prior exposure to a proteasome inhibitor (PI) 108. Documented response of at least partial response (PR) to at least 1 prior line of therapy 109. Measurable disease, with at least 1 of the following assessed at a central laboratory within the 21 days prior to randomization: a. Serum M-protein = 0.5 g/dL b. Urine M-protein = 200 mg/24 hours c. 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 110. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 111. Left ventricular ejection fraction (LVEF) = 40% within the 21 days prior to randomization 112. Adequate organ and bone marrow function performed at a central laboratory within the 21 days prior to randomization, defined by: a. Bilirubin 50%. Subjects must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count.) f. Calculated or measured creatinine clearance (CrCl) of = 30 mL/min. Calculation must be based on the Cockcroft and Gault formula: [(140 – Age) × Mass (kg) / (72 × Creatinine mg/dL)]; multiply result by 0.85 if female 113. Females of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test performed at a central laboratory, within the 21 days prior to randomization, and must not be breastfeeding. 114. Females of childbearing potential must agree to use highly effective method(s) of contraception, during the study and for 30 days following the last study drug administration. (Refer to Appendix K for specific contraceptive requirements). 115. Male subjects who are sexually active with an FCBP must agree to use condoms (unless they have had a vasectomy with medical confirmation of surgical success), during treatment and for an additional 90 days following the last study drug administration.
Exclusion criteria
Exclusion criteria: 201. Waldenström macroglobulinemia 202. Multiple myeloma of Immunoglobulin M (IgM) subtype 203. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 204. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential) 205. Myelodysplastic syndrome 206. Second malignancy within the past 5 years except: a. Adequately treated basal cell or squamous cell skin cancer b. Carcinoma in situ of the cervix c. Prostate cancer 95% five-year disease-free survival 207. History of or current amyloidosis 208. Cytotoxic chemotherapy or other antineoplastic therapy, aside from immunotherapy or proteasome inhibitors, within the 28 days prior to randomization 209. Immunotherapy, such as an IMiD, or a proteasome inhibitor, within the 21 days prior to randomization 210. Glucocorticoid therapy exceeding a cumulative dose of 160 mg dexamethasone or equivalent, within the 14 days prior to randomization 211. Radiation therapy: a. Focal therapy within the 7 days prior to randomization b. Extended field therapy within the 21 days prior to randomization 212. Prior treatment with either carfilzomib or oprozomib 213. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) 214. Contraindication to dexamethasone or any of the required concomitant medications or supportive treatments 215. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV, refer to Appendix F), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 6 months prior to randomization 216. Active infection requiring systemic treatment within the 14 days prior to randomization 217. Pleural effusions requiring thoracentesis within the 14 days prior to randomization 218. Ascites requiring paracentesis within the 14 days prior to randomization 219. Ongoing graft-versus-host disease 220. Uncontrolled hypertension or diabetes mellitus 221. Significant neuropathy (= Grade 3) within the 14 days prior to randomization 222. Known cirrhosis 223. Known human immunodeficiency virus (HIV) seropositivity, hepatitis C infection, or hepatitis B infection. Subjects with past hepatitis B virus infection, defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen (anti-HBc) antibody test, are eligible. Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 224. Participation in another interventional study within the 28 days prior to randomiz
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of once weekly carfilzomib dosing in combination with dexamethasone to the PFS of twice weekly carfilzomib dosing in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma who have received prior treatment with a proteasome inhibitor and an IMiD (immunomodulatory agent).; Secondary Objective: - Overall response rate (ORR) - Overall survival (OS) - Safety and tolerability - Pharmacokinetics (PK) of carfilzomib using sparse sampling ;Primary end point(s): The primary endpoint is PFS, which is defined as the time in months from randomization to the earlier of disease progression or death due to any cause.;Timepoint(s) of evaluation of this end point: The final PFS analysis will be conducted when approximately 350 PFS events have occurred or by end of year 2018, whichever is earlier. A total of 350 PFS events will provide 83% power to detect a significant difference in PFS between the 2 treatment groups with 1 interim analysis if the underlying HR is 0.73. The interim analysis will be performed when approximately 75% of the total PFS events (i.e., 263 events) have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are as follows: - ORR, defined as the proportion of subjects who achieved a confirmed PR, VGPR, CR, or sCR, according to the IMWG-URC. - OS defined as the time in months from randomization to death due to any cause. - Safety and tolerability - Sparse PK ; Timepoint(s) of evaluation of this end point: - ORR will be analyzed at the time of the PFS analysis (interim or final), only if the PFS analysis crosses the boundary. - The analysis of OS will be conducted at the time of the PFS analysis (interim or final), only if both PFS and ORR analyses are positive | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Romania, Slovakia, Spain, Sweden, United Kingdom
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed