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-AT
- 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 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
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 significant volume of bone marrow within 28 days
prior to rando
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with<br>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<br>*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<br>response of stringent complete response [sCR], complete response<br>[CR], very good partial response [VGPR], and partial response [PR] per<br>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 Outcome Measures
Name Time Method Secondary end point(s): * PFS over the duration of the study <br>*convenience as measured by the<br>Patient-reported Convenience With<br>Carfilzomib-dosing Schedule Question<br>after cycle 4 of treatment;Timepoint(s) of evaluation of this end point: *1-year PFS<br>*convenience as measured by the<br>Patient-reported Convenience With<br>Carfilzomib-dosing Schedule Question<br>after cycle 4 of treatment