E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma |
Multiple Myeloma |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Myeloma |
Multiple Myeloma |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 plasmacytoma 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 | 2 |
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 |
Denmark |
Netherlands |
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 |