A study comparing carfilzomib (study drug) given in combination with dexamethasone once a week to twice-weekly carfilzomib in combination with dexamethasone, at the same dose, in patients with cancer of plasma cells which has re-occurred after previous successful treatment or did not show any improvement under previous treatment.
- Conditions
- Multiple MyelomaMedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005325-12-DK
- Lead Sponsor
- Onyx Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 460
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 freelight 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 < 1.5 times the upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN
c. Absolute neutrophil count (ANC) = 1 × 109/L (screening ANC must be independent of growth factor support for = 7 days)
d. Hemoglobin = 8 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusions per institutional guidelines are allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining the screening hemoglobin.)
e. Platelet count = 50,000/mm3 (= 30,000/mm3 if myeloma involvement in the bone marrow is > 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 addition
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 < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
d. Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
e. Treated medullary or papillary thyroid cancer
f. Similar condition with an expectation of > 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 w
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method