Multiple Myeloma MedDRA version: 18.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Carfilzomib
Product Code: PR-171
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Carfilzomib
CAS Number: 868540-17-4
Current Sponsor code: PR-171
Other
506160 - CARFILZOMIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 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 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 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.) 24. Participation in another interventional study within the 28 days prior to randomization 25. Major surgery (except kyphoplasty) within the 28 days prior to randomization 26. Female subjects who are pregnant or lactating 27. Any other clinically significant medical disease or social condition that, in the investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent, be compliant with study procedures, or provide accurate information.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the ORR between once-weekly carfilzomib dosing in combination with dexamethasone to twice-weekly carfilzomib dosing in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma who have received prior treatment with bortezomib and an IMiD;Secondary Objective: ? Progression-free survival (PFS) ? Overall survival (OS) ? Safety and tolerability ? Pharmacokinetics (PK) of carfilzomib using sparse sampling;Primary end point(s): The primary endpoint is ORR, which is defined as the proportion of subjects who achieved a confirmed PR, VGPR, CR, or sCR according to the IMWG-URC;Timepoint(s) of evaluation of this end point: * Assessment every 4 weeks to collect lab-data (Blood and Urine) for response assessment bone-marrow biopsy (only once) in case of to confirm CR/sCR or if progression in bone-marrow plasma-cell – percentage suspected. If baseline soft tissue plasmacytoma present, repetition of this imaging if progressive disease suspected clinically or to confirm MR or better in case of given clinical evidence. All these until progressive disease is demonstrated o After discontinuation of study drug treatment and demonstration of disease progression, survival follow up every 3 months (short questionnaire may be done via telephone-call) until death confirmed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are as follows: ? PFS defined as the time in months from randomization to the earlier of disease progression or death due to any cause. ? OS defined as the time in months from randomization to death due to any cause. ? Safety and tolerability;Timepoint(s) of evaluation of this end point: • Interim analysis of PFS is expected to occur at the time of analysis of ORR, approximately 19 months after the first subject is randomized. Final PFS analysis is expected to occur approximately 25 months after the first subject is randomized. • Interim analysis of OS is expected to occur at the time of analysis of ORR, approximately 19 months after the first subject is randomized. Final OS analysis is expected to occur approximately 25 months after the first subject is randomized. • Data will be collected till 30 days after the last administration of study treatment.nter information in English and add any other language that is applicable | — |
Countries
Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Monitor Sanjay Aggarwal, MD
Onyx Therapeutics
Outcome results
None listed