E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067095 |
E.1.2 | Term | Multiple myeloma progression |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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 |
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E.4 | Principal 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:
o Absolute neutrophil count (ANC) < 1.0 × 109/L
o Hemoglobin < 5 mmol/L (<80 g/L) (prior RBC transfusion or recom-binant human erythropoietin use is permitted)
o Platelet count < 50 × 109/L (< 30 × 109/L if myeloma involvement in the bone marrow is > 50%)
o Serum ALT or AST > 3.5 times the upper limit of normal and serum direct bilirubin > 34 µmol/L (2 mg/dL)
o Creatinine 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-points:
• 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).
• Comparison of TTP between carfilzomib-dexamethasone maintenance and observation in patients treated with a second HDT.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After induction treatment, two months after highdose therapy and after maintenance therapy |
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E.5.2 | Secondary end point(s) |
Secondary end-points:
• Toxicity of CAR-CY-DEX as induction regime and carfil-zomib as part of the high-dose melphalan conditioning
• Response rates of induction therapy and HDT
• Time to marrow regeneration (neutrophil- and platelet recov-ery) after the HDT
• Toxicity of maintenance treatment with carfilzomib-dexamethasone
• Comparison of overall survival between carfilzomib-dexamethasone maintenance and observation in patients treated with a second HDT • Quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After induction treatment, two months after highdose therapy and after maintenance therapy |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
observation without treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |