Relapsed or Refractory Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Kyprolis
Product Name: Carfilzomib Lyophilisate for Solution for Injection
Product Code: PR-171
Pharmaceutical Form: Powder for solution for
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: *Subject has provided informed consent prior to initiation of any study-specific activities or procedures or subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent. *Males or females = 18 years of age. *Documented relapse or progressive multiple myeloma on or after any treatment (subjects refractory to the most recent line of therapy are eligible, unless last treatment contained PI or lenalidomide and dexamethasone). *Subjects must have at least PR to at least 1 line of prior therapy. *Subjects must have received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation maintenance therapy will be considered as 1 line of therapy). See Section 12.8 for guidelines for documenting prior treatment. *Prior therapy with a PI or lenalidomide and dexamethasone is allowed, as long as the patient had at least a PR to most recent therapy with PI or lenalidomide and dexamethasone, was not removed due to toxicity, and will have at least a 6-month PI or lenalidomide and dexamethasone treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with lenalidomide during this 6-month PI or lenalidomide and dexamethasone treatment-free interval). *Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as long as the subject did not progress during the first 3 months after initiating lenalidomide and dexamethasone containing therapy. Measurable disease with at least 1 of the following assessed within 21 days prior to randomization: ? IgG multiple myeloma: serum monoclonal protein (M-protein) level = 1.0 g/dL ? IgA, IgD, IgE multiple myeloma: serum M-protein level = 0.5 g/dL ? urine M-protein = 200 mg per 24 hours ? 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 *Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 ? 2 (see Section 12.9). 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 230 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: Disease-related *Waldenström macroglobulinemia. *Multiple myeloma of IgM subtype. *POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). *Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential). *Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met). *Myelodysplastic syndrome. Other Medical Conditions *History of other malignancy within the past 5 years, with the following exceptions: ? Malignancy treated with curative intent and with no known active disease present for = 3 years before enrollment and felt to be at low risk for recurrence by the treating physician ? Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease ? Adequately treated cervical carcinoma in situ without evidence of disease ? Adequately treated breast ductal carcinoma in situ without evidence of disease ? Prostatic intraepithelial neoplasia without evidence of prostate cancer ? Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ ? Treated medullary or papillary thyroid cancer ? Similar neoplastic conditions with an expectation of > 95% 5-year disease-free survival *Known HIV infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy are allowed). Tests to be performed if required per local country regulations. *Ongoing graft-vs-host disease. *Acute active infection requiring systemic antibiotics, antifungal, antiviral (except antiviral therapy directed at hepatitis B) agents within 14 days prior to randomization. *Known cirrhosis. *Significant neuropathy (grades 3 to 4, or grade 2 with pain) within 14 days prior to randomization. *Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization. Cardiopulmonary Conditions *Uncontrolled hypertension, defined as an average systolic blood pressure = 160 mmHg or diastolic = 100 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology 2013 guidelines; Section 12.10). *Active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: *compare progression-free survival (PFS) between treatment arms *compare patient-reported convenience with carfilzomib-dosing schedule between treatment arms ;Timepoint(s) of evaluation of this end point: Over the duration of the study; Main Objective: compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with RRMM with 1 to 3 prior lines of therapy ; Primary end point(s): 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] per International Myeloma Working Group Uniform Response Criteria [IMWG-URC]) over the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): *1-year PFS *convenience as measured by the Patient-reported Convenience With Carfilzomib-dosing Schedule Question after cycle 4 of treatment ; Timepoint(s) of evaluation of this end point: *1-year PFS *convenience as measured by the Patient-reported Convenience With Carfilzomib-dosing Schedule Question after cycle 4 of treatment | — |
Countries
Bulgaria, Canada, Czech Republic, France, Germany, Greece, Japan, Korea, Republic of, Netherlands, Romania, Russian Federation, Spain, Sweden, Turkey, United States
Contacts
Public ContactIHQ Medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed