Study of Carfilzomib in Multiple Myeloma Relapsed After High-dose Melphalan With Autologous Stem Cell Support

Inclusion Criteria:

* Myeloma diagnosis according to IMWG criteria
* First treatment demanding relapse after HDT according to IMWG criteria
* More than 2.0 x 10m 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

Exclusion Criteria:

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:

  * Absolute neutrophil count (ANC) \< 1.0 × 109/L
  * Hemoglobin \< 5 mmol/L (\<80 g/L) (prior RBC transfusion or recombinant human erythropoietin use is permitted)
  * Platelet count \< 50 × 109/L (\< 30 × 109/L if myeloma involvement in the bone marrow is \> 50%)
  * Serum ALT or AST \> 3.5 times the upper limit of normal and serum direct bilirubin \> 34 µmol/L (2 mg/dL)
  * Creatinine clearance (CrCl) \< 15 mL/minute, either measured or calculated 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, dexamethasone 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, uncontrolled angina, clinically significant pericardial disease, uncontrolled severe arrhythmias, 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