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-PL
- Lead Sponsor
- Onyx Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 415
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 < 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
pregna
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
2
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