Phase II study of carfilzomib- cyclophosphamide-dexamethasone and high-dose melphalan followed by randomization between observa-tion or maintenance with carfil-zomib and dexamethasone in pa-tients with relapsed multiple myeloma after high-dose melphalan with autologous stem cell support
- Conditions
- Multiple MyelomaMedDRA version: 17.1Level: LLTClassification code 10067095Term: Multiple myeloma progressionSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2013-003789-15-NO
- Lead Sponsor
- ordic Myeloma Study Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
•Myeloma diagnosis according to IMWG criteria
•First treatment demanding relapse after HDT according to IMWG criteria
•More than 2.0 x 106 CD34+ stem cells / kg body weight in the freezer for stem cell support
•Signed informed consent given prior to any study related activities have been performed
•Age > 18 years
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
Demographic
•Allogeneic transplantation scheduled as a part of the treatment
•Treatment demanding relapse less than one year after HDT
•Myeloma treatment after the first HDT, except radiotherapy, bisphosphonates, denosumab and corticosteroids less than 6 days for symptom control
•Patients not having received HDT as first line treatment
•Previous treatment with carfilzomib
•Expected survival of less than six months
•Performance status (WHO) = 3
Laboratory
•Serum M-component < 5 g/l and urine M-component < 200 mg/l
•Any of the following laboratory abnormalities:
oAbsolute neutrophil count (ANC) < 1.0 × 109/L
oHemoglobin < 5 mmol/L (<80 g/L) (prior RBC transfusion or recom-binant human erythropoietin use is permitted)
oPlatelet count < 50 × 109/L (< 30 × 109/L if myeloma involvement in the bone marrow is > 50%)
oSerum ALT or AST > 3.5 times the upper limit of normal and serum direct bilirubin > 34 µmol/L (2 mg/dL)
oCreatinine clearance (CrCl) < 15 mL/minute, either measured or cal-culated using a standard formula
Concurrent conditions
•Concurrent disease making treatment with carfilzomib, cyclophosphamide or dexamethasone unsuitable
•Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to enrolment
•Major surgery within 21 days prior to enrolment
•Acute active infection requiring treatment
•Known or suspected hypersensitivity or intolerance to melphalan, dexa-methasone or Captisol® (a cyclodextrin derivative)
•Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, NYHA Class III or IV heart failure, uncon-trolled angina, clinically significant pericardial disease, uncontrolled severe arrhytmias, or cardiac amyloidosis
•LVEF <40%, determined by 2-D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA)
•Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrolment
•Serious hepatic disorder, including active hepatitis B or C infection
•Other serious medical or psychiatric illness likely to interfere with participation in this clinical study
•Use of any investigational agents or experimental medical device within 28 days prior to enrolment into the study
Ethical/other
•Pregnant or lactating females
•Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception
•Male subjects must agree to practice contraception
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The purpose of our study is to evaluate the effect of the combination of carfilzomib, cyclophosphamide and dexamethasone in the induction regimen and carfilzomib in the conditioning regimen of salvage HDT. In addition to evaluate the potential effect of carfilzomib/dexamethasone maintenance treatment. ;Secondary Objective: Not applicable;Primary end point(s): Primary end-points:<br>•Comparison of time to progression (TTP) after first high-dose melphalan with stem cell support (HDT) and TTP after a second HDT combined with carfilzomib-cyclophosphamide-dexamethasone (CAR-CY-DEX).<br>•Comparison of TTP between carfilzomib-dexamethasone maintenance and observation in patients treated with a second HDT.<br><br> <br><br>;Timepoint(s) of evaluation of this end point: After induction treatment, two months after highdose therapy and after maintenance therapy
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary end-points:<br>•Toxicity of CAR-CY-DEX as induction regime and carfil-zomib as part of the high-dose melphalan conditioning<br>•Response rates of induction therapy and HDT<br>•Time to marrow regeneration (neutrophil- and platelet recov-ery) after the HDT<br>•Toxicity of maintenance treatment with carfilzomib-dexamethasone<br>•Comparison of overall survival between carfilzomib-dexamethasone maintenance and observation in patients treated with a second HDT •Quality of life;Timepoint(s) of evaluation of this end point: After induction treatment, two months after highdose therapy and after maintenance therapy