A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination with Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
- Conditions
- Relapsed or Refractory Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000665-36-BG
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 460
*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 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
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 subject whose blood pressure is greater than or equal to = 160 mmHg - systolic or greater than or equal to = 100 mmHg diastolic when taken in accordance with the European Society of Hypertension/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 significant volume o
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