E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple myeloma at first presentation |
Multipel myeloom |
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E.1.1.1 | Medical condition in easily understood language |
Multiple myeloma |
Multipel myeloom, ziekte van Kahler |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the feasibility and efficacy of carfilzomib in combination with thalidomide and dexamethasone in patients with Multiple Myeloma at first presentation. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate the clinical efficacy of carfilzomib in combination with thalidomide and dexamethasone for response in remission induction of Multiple Myeloma at first presentation.
- To investigate the clinical efficacy of carfilzomib in combination with thalidomide and dexamethasone for response in consolidation treatment of Multiple Myeloma at first presentation.
- To assess the stem cell harvest following carfilzomib in combination with thalidomide and dexamethasone
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon & Durie criteria (see appendix I);
· Age 18-65 years inclusive;
· WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and
not by co-morbid conditions) (see appendix II);
· Negative urine pregnancy test at inclusion if applicable;
· Written informed consent.
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E.4 | Principal exclusion criteria |
· Known intolerance of Thalidomide;· Systemic AL amyloidosis;· Non-secretory MM;· Waldenstrom’s macroglobulinemia or IgM MM;· Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone or local radiotherapy in case of local myeloma progression;· Severe cardiac dysfunction (NYHA classification II-IV, see appendix);· Significant hepatic dysfunction (serum bilirubin ³ 30 mmol/L or transaminases ³ 2.5 times normal level), unless related to myeloma;· Creatinine clearance (measured or calculated) <30cc/min· Alkaline Phosphatase >3x ULN· ANC < 1,0 x109/L, platelets < 75 x109/L, Hb < 4.9 mmol/L· Non-secretory MM defined as SPEP < 5 g/L and UPEP < 200 mg/24 hr· Intolerance to thromboprophylaxis;· Patients known to be HIV-positive;· Patients with active, uncontrolled infections;· Patients with neuropathy, CTC grade 3 or higher, or grade 2 painful peripheral neuropathy;· Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;· Patients (all males and all pre-menopausal women) who are not willing or capable to use adequate contraception during the therapy;· Lactating women;· WHO Performance status > 3. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response (Complete response (CR), very good partial response (VGPR), overall response (OR)):After induction prior to HDM/ASCTAfter HDM/ASCT prior to consolidation treatmentAt end of consolidation treatment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
after induction
after HDM/ASCT
after consolidation |
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E.5.2 | Secondary end point(s) |
Efficacy and toxicity of induction treatment;
Efficacy and toxicity of consolidation treatment;
Feasibility of good quality stem cell harvest;
Progression-free survival (PFS);
Overall Survival (OS). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
These endpoints will be evaluated when applicable data for all patients
are available |
|
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 | Yes |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |