Relapsed or Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
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 after last 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 is allowed if the patient achieved at least a PR to the most recent therapy with a PI, did not relapse within 60 days of discontinuation, and PI was no removed due to toxicity * Prior therapy with a lenalidomide and dexamethasone is allowed if the patient achieved at least a PR to the most recent therapy with lenalidomide and dexamethasone, did not progress within 3 months of a lenalidomide and dexamethasone-containing treatment, did not relapse within 60 days of discontinuation of treatment, and treatment was no removed due to toxicity • History of prior neuropathy is permitted if not exceeding grade 2 which has either resolved within 14 days of enrollment or if ongoing is = grade 1), • Patients are permitted to have received single agent lenalidomide as maintenance therapy during the 6-months prior to first study treatment. * Measurable disease with at least 1 of the following assessed within 28 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 permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study). *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 subject whose blood pressure exceeds = 160 mmHG - systolic or = 100mmHg diastolic when taken in accordance with the European Society of hypertensions/European Society of cardiology 2018 guidelines. (Section 12.10; Williams et al, 2018). *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. *Intolerance to hydration due to pre-existing pulmonary or cardiac impairment. *History of interstitial lung disease or ongoing interstitial lung disease. Prior/Concomitant Therapy *Immunotherapy within 28 days prior to randomization. *Monoclonal antibody therapy within 28 days prior to randomization. *Chemotherapy with approved anticancer therapeutic within 28 days prior to randomization. *Glucocorticoid therapy within 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or equivalent dose of other corticosteroids. *Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a sign
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;Secondary Objective: *compare progression-free survival(PFS) between treatment arms *compare patient-reported convenience with carfilzomib-dosing schedule between treatment arms;Primary end point(s): overall response (OR, 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;Timepoint(s) of evaluation of this end point: Over the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): * PFS over the duration of the study *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
Austria, Bulgaria, Canada, Czechia, Czech Republic, Finland, France, Germany, Greece, Japan, Lithuania, Netherlands, Romania, Russian Federation, Slovakia, Spain, Sweden, Turkey, United States
Contacts
Public ContactMedical Information the Netherlands
Amgen Nederland
Outcome results
None listed