Multiple myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000054086
Conditions
Interventions
Trade Name: Kyprolis
Product Name: Carfilzomib
Product Code: PR-171
Pharmaceutical Form: Powder for solution for infusion
INN or Propose
506160
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Trade Name: Velcade
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Multiple myeloma with relapsing or progressing disease at study entry. 2.Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization): •Serum M-protein = 0.5 g/dL, or •Urine M-protein = 200 mg/24 hour, or •In patients without detectable serum or urine M-protein, serum free light chain (FLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lambda ratio, or •For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) = 750 mg/dL (0.75 g/dL). 3.Patients must have documented at least PR to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment. 4. Received at least 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/ maintenance therapy will be considered as one line of therapy). 5. Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval). 6. Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to prior carfilzomib therapy, was not removed from carfilzomib therapy due to toxicity, and had at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month carfilzomib treatment-free interval). The exception to this are patients randomized or previously randomized in any other Onyx-Sponsored Ph 3 trial 7.Males and females = 18 years of age. 8. ECOG Performance Status of 0 to 2. 9. Adequate hepatic function within 21 days prior to randomization, with bilirubin 50%) within 21 days prior to randomization. Patients should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count. 14. Calculated or measured CrCl of = 15 mL/min within 21 days prior to randomization. Calculation should be based on standard formula such as the Cockcroft and Gault: [(140 – Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female. 15. Written informed consen
Exclusion criteria
Exclusion criteria: 1. Multiple myeloma of IgM subtype. 2. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization. 3. POEMS syndrome. 4. Plasma cell leukemia or circulating plasma cells = 2 × 109/L. 5. Waldenstrom’s Macroglobulinemia. 6. Patients with known amyloidosis. 7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization. 8. Patients randomized or previously randomized in any other Onyx-sponsored Phase 3 trial. 9. Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow). 10. Immunotherapy within 21 days prior to randomization. 11. Major surgery (except kyphoplasty) within 28 days prior to randomization. 12. Active congestive heart failure (NYHA Class III to IV; refer to Appendix H), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization. 13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization. 14. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen [SAg] and core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed). 15. Patients with known cirrhosis. 16. Second malignancy within the past 3 years except: - adequately treated basal cell or squamous cell skin cancer - carcinoma in situ of the cervix - prostate cancer Gleason score = 6 with stable prostatespecific antigen (PSA) over 12 months - breast carcinoma in situ with full surgical resection - treated medullary or papillary thyroid cancer 17. Patients with myelodysplastic syndrome. 18. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization. 19. Female patients who are pregnant or lactating. 20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) 21. Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol. 22. Patients with contraindication to dexamethasone. 23. Contraindication to any of the required concomitant drugs or supportive treatments,including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment. 24. Ongoing graft-vs-host disease. 25. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization. 26. Any other clinically significant medical disease or psychiatric condition that, in the Investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) in patients with multiple myeloma relapsed after 1 to 3 prior therapies treated with either carfilzomib plus dexamethasone (Cd) or bortezomib (Velcade®) plus dexamethasone (Vd).; Secondary Objective: To compare the following between the treatment groups: - Overall Survival (OS) - Overall Response Rate (ORR) [defined as the proportion of best overall response of stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)] - Duration of Response (DOR) - Neuropathy Events (defined from Grade 2 or higher peripheral neuropathy) - Safety and Tolerability -Assess changes from baseline in LVEF, RV function, and pulmonary artery pressure in a subset of patients from both treatment groups ;Primary end point(s): The primary endpoint is PFS by Independent Review Committee (IRC);Timepoint(s) of evaluation of this end point: Study is expected to have required number of PFS events approximately 8 months after enrollment is complete | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: •Overall survival •Overall Response Rate (defined as the proportion of best overall response of sCR, CR, VGPR, and PR) •Duration of Response •Neuropathy Events (defined from Grade 2 or higher peripheral neuropathy) •Safety and Tolerability: -Change from baseline in LVEF, RV function, and pulmonary artery pressure in a subset of patients from both treatment groups ; Timepoint(s) of evaluation of this end point: Secondary end points are to be evaluated at the time of the final OS analysis when the required number of events have been reached, estimated at approximately 78 months after the enrollment start. | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Singapore, Slovakia, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed