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: 18.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005325-12-GR
- Lead Sponsor
- Onyx Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 460
1. Age = 18 years
2. Able to provide written informed consent in accordance with federal, local, and institutional
guidelines
3. Relapsed multiple myeloma
4. Refractory multiple myeloma defined as meeting 1 or more of the following:
a. Nonresponsive to most recent therapy (stable disease only or PD while on treatment), or
b. Disease progression within 60 days of discontinuation from most recent therapy
5. At least 2 but no more than 3 prior therapies for multiple myeloma
6. Prior exposure to an immunomodulatory agent (IMiD)
7. Prior exposure to a proteasome inhibitor (PI)
8. Documented response of at least partial response (PR) to 1 line of prior therapy
9. Measurable disease with at least 1 of the following assessed 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 detectable serum or urine M-protein, serum free light chain (SFLC) = 100
mg/L (involved light chain) and an abnormal serum kappa lambda ratio
10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
11. Left ventricular ejection fraction (LVEF) = 40% within the 21 days prior to randomization
12. Adequate organ and bone marrow function 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) = 1000/mm3 (screening ANC should be independent of growth
factor support for = 1 week)
d. Hemoglobin = 8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC]
transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may
not have been done within 7 days
prior to obtaining screening hemoglobin.)
e. Platelet count = 50,000/mm3 (= 30,000/mm3 if myeloma involvement in the bone marrow is > 50%.
Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the
screening platelet count.)
f. Calculated or measured creatinine clearance (CrCl) of = 30 mL/min
Calculation should be based on the Cockcroft and Gault formula:
[(140 – Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female
13. Females of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test
within the 21 days prior to randomization (performed at a central laboratory).
14. Females of childbearing potential and male subjects who are sexually active with
FCBP must agree to use effective concomitant method(s) of contraception during
the study and for 30 days following the last study drug treatment administration.
Are the trial subjects under 18? no
Number
1. Waldenström macroglobulinemia
2. Multiple myeloma of Immunoglobin M (IgM) subtype
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin
changes)
4. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
5. Myelodysplastic syndrome
6. 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
7. History of or current amyloidosis
8. Cytotoxic chemotherapy within the 28 days prior to randomization
9. Immunotherapy within the 21 days prior to randomization
10. Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative
dose of 160 mg of dexamethasone or 1000 mg prednisone
11. Radiation therapy:
a. Focal therapy within the 7 days prior to randomization
b. Extended field therapy within the 21 days prior to randomization
12. Prior treatment with either carfilzomib or oprozomib
13. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
carfilzomib)
14. Contraindication to dexamethasone or any of the required concomitant drugs or supportive
treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to
pre-existing pulmonary or cardiac impairment
15. 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 enrollment
16. Active infection within the 14 days prior to randomization requiring systemic antibiotics
17. Pleural effusions requiring thoracentesis within the 14 days prior to randomization
18. Ascites requiring paracentesis within the 14 days prior to randomization
19. Ongoing graft-versus-host disease
20. Uncontrolled hypertension or uncontrolled diabetes despite medication
21. Significant neuropathy (= Grade 3) within the 14 days prior to randomization
22. Known cirrhosis
23. Known human immunodeficiency virus (HIV) seropositivity, hepatitis C infection,
or hepatitis B infection (subjects with past hepatitis B virus (HBV) infection or
resolved HBV infection defined as having a negative HBsAg test and a positive
antibody to hepatitis B core
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