E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed symptomatic Multiple Myeloma |
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E.1.1.1 | Medical condition in easily understood language |
Newly diagnosed symptomatic Multiple Myeloma |
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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 | 20.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the feasibility, defined as discontinuation rate, of a dose-adapted MPV scheme in MM patients ≥ 75 years of age |
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E.2.2 | Secondary objectives of the trial |
• To assess toxicity
• To assess efficacy determined as response rate, PFS and OS
• To assess time to response
• To assess the relative dose intensity of MPV
• To assess the cumulative dose intensity of MPV
• To assess the predictive value of geriatric assessments, biomarkers reflecting biological age and sarcopenia with respect to feasibility and efficacy
• To assess QoL
• To analyze the value of polymorphism of genes involved in drug metabolism in predicting bortezomib-induced PNP
• To assess the prognostic value of risk factors at diagnosis, including β2-microglobulin and chromosomal abnormalities
• To analyze the prognostic value of myeloma gene expression profiles
• Cost effectiveness analysis
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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 (see appendix A)
- Age ≥ 75 years
- WHO performance status 0-3, WHO 4 performance status is allowed when related to MM (see appendix E)
- Measurable disease as defined by the presence of M-protein in serum or urine or proven plasmacytoma by biopsy (see appendix A for definitions) (If plasmacytoma is the only measurable parameter, the patient is not allowed to be included in the study, because of difficult response evaluation).
-Patient gives consent for extra bone marrow, blood and skin biopsy sampling.
-Written informed consent
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E.4 | Principal exclusion criteria |
- Non-secretory MM
- Systemic Amyloid Light-chain (AL) amyloidosis
- Polyneuropathy, grade 1 with pain or grade ≥ 2
- Severe cardiac dysfunction (NYHA classification IV, appendix F)
- Severe pulmonary dysfunction defined as breathlessness at rest
- Significant hepatic dysfunction (total bilirubin ≥ 30 μmol/l or transaminases ≥ 3 times normal level), unless related to MM
- Renal insufficiency requiring dialysis
- Patients with active, uncontrolled infections
- Pre-treatment with cytostatic drug, imunnomodulatory drugs (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 Human Immunodeficiency Virus (HIV)-positive
- Active malignancy other than MM requiring treatment or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Patients with plasma cell leukemia |
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E.5 End points |
E.5.1 | Primary end point(s) |
Discontinuation rate, defined as the proportion of patients who received less than 9 cycles of MPV according to protocol treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation of this endpoint will take place as soon as the relevant data of all patients are available and validated. |
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E.5.2 | Secondary end point(s) |
- 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 4.0
- Overall response rate where response is defined as sCR, CR, VGPR or PR
- Time to response
- Progression free survival , defined as time from registration to progression, relapse or death from any cause whichever occurs first
- Overall survival, measured from time of registration to death. Patients still alive or lost to follow up are censored at the date they were last known to be alive (date last contact)
- Relative dose intensity and cumulative dose intensity of Melphalan, Prednisone and Bortezomib
- Predictive value of geriatric assessments
- Quality of life as defined by the EORTC QLQ-C30 and MY-20 definitions
- Association of biomarkers for biological age with toxicity and feasibility of the treatment
- Associations with toxicity and with feasibility of the treatment regimen of polymorphism of genes involved in drug metabolism and related with bortezomib-induced PNP
- Association of risk factors and myeloma gene expression profiles with prognosis
- Cost effectiveness as defined by the EQ-5D and the involved costs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation of this endpoint will take place as soon as the relevant data of all patients are available and validated. |
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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 | 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 | No |
E.8.1.2 | Open | No |
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 | No |
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 | 65 |
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 | No |
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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |