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] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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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 compare progression free survival with Melphalan/Prednisone (MP)-Thalidomide followed by thalidomide maintenance versus MP-Lenalidomide followed by maintenance with lenalidomide
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E.2.2 | Secondary objectives of the trial |
- To compare (stringent) complete and very good partial response with MP-Thalidomide versus MP-Lenalidomide
- To compare overall survival with MP-Thalidomide versus MP-Lenalidomide
- To assess and compare overall response* with MP-Thalidomide versus MP-Lenalidomide
- To assess time to maximum response with MP-Thalidomide versus MP-Lenalidomide
- To assess the effect of maintenance therapy with thalidomide alone following MP-Thalidomide induction or lenalidomide following MP-Lenalidomide, in terms of improvement of response
- To assess and compare the time from relapse/progression (after initial response) to death in patients having been treated with MP-Thalidomide versus MP-Lenalidomide
- To assess the impact on the quality of life of thalidomide compared with lenalidomide
- To assess the safety and toxicity of induction of both regimens
* overall response will be defined as (stringent) complete response, very good partial response and partial response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Previously untreated patients with a confirmed diagnosis of symptomatic multiple myeloma according to IMWG criteria
- Age > 65 years or patients ≤ 65 not eligible for high dose chemotherapy and peripheral stem cell transplantation
- WHO performance status 0-3 for patients <75 years and WHO performance status 0-2 for patients ≥75 years
- Measurable disease as defined by the presence of M-protein in serum or urine or proven plasmocytoma by biopsy
- Written informed consent
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E.4 | Principal exclusion criteria |
- Non-secretory MM
- Known hypersensitivity to thalidomide
- Systemic AL amyloidosis
- Polyneuropathy, grade 2 or higher
- Severe cardiac dysfunction (NYHA classification II-IV)
- Severe pulmonary dysfunction
- Significant hepatic dysfunction (total bilirubin ≥30 umol/l or transaminases ≥3 times normal level), unless related to myeloma
- Creatinine clearance < 30 ml/min
- Patients with active, uncontrolled infections
- Pre-treatment with cytostatic drug, IMIDs or proteasome inhibitors. Radiotherapy or a short course of steroids (e.g. 4 day treatment of dexamethasone 40 mg/day or equivalent) are allowed.
- Patients known to be HIV-positive
- History of active malignancy during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
- Not able and/or not willing to use adequate contraception
- Pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
- Progression free survival, defined as time from registration to progression or death from any cause
- Response rate (sCR, CR or VGPR)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After cycle 1; 3; 5 ; 7; 9 & every three months during maintenance and every 6 months during Follow-Up. |
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E.5.2 | Secondary end point(s) |
•Overall response rate defined as sCR, CR, VGPR or PR
•Overall survival, measured from time of registration
•Quality of response during maintenance, measured as improvement of response (from start maintenance till progression)
•Time to maximum response, defined as time from registration to maximum response
•Time to death from relapse/progression (after initial response), measured from time of first relapse/progression
•Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria (CTC), version 3.0
•Quality of life as defined by the EORTC QLQ-C30 definitions.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- After cycle 1; 3; 5 ; 7; 9 & every three months during maintenance and every 6 months during Follow-Up.
- Quality of life: at baseline; after cycle 3; 9; after 6 and 12 months maintenance & off treatment. |
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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 | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 70 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Norway |
Sweden |
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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 | 15 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 15 |
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 |