E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
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 compare the efficacy of the combination of lenalidomide with low-dose alkylating agents versus high-dose melphalan in newly diagnosed, symptomatic MM patients. |
|
E.2.2 | Secondary objectives of the trial |
- To assess the safety of lenalidomide with low-dose alkylating agents compared to high-dose melphalan in newly diagnosed, symptomatic MM patients. - To assess the prognostic value of risk factor at diagnosis (β2-microglobulin, albumin, C-reactive protein, cytogenetics). - To assess the efficacy and safety of lenalidomide as maintenance treatment after the consolidation phase. - To assess prognostic significance of stringent remission evaluated by free light chain assay |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Sottostudio osservazionale dei pazienti asintomatici
|
|
E.3 | Principal inclusion criteria |
-Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements. -Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. -Patient is 65 years old or younger at the time of signing the informed consent -Women of child-bearing potential must agree to use 2 methods of contraception: 1 effective (for example hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before starting the therapy, during the Treatment Period, and for 4 weeks after the last dose of lenalidomide -Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy. -Negative serum B-human chorionic gonadotropin (B-HCG) pregnancy test both 24 hours prior to beginning of therapy and then at 4 weeks intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles during study treatment for subjects of childbearing potential -Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (10), and has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours; measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells >10%. -Patient has a Karnofsky performance status ≥ 60%. -Patient has a life-expectancy > 6 months -Patient has HBV, HCV and HIV negative test. -Patients must have normal ECG and NYHA ≤ 2; an evaluation of ejection fraction by ECHO or MUGA is optional -Patients must normal chest X ray; an evaluation of pulmonary function studies on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) is optional. -Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1): *Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test. *Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without the use of growth factors. *Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L). *Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN). *Alanine transaminase (ALT): ≤ 2.5 x the ULN. *Total bilirubin: ≤ 1.5 x the ULN. *Calculated or measured creatinine clearance: ≥ 20 mL/minute -Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized. |
|
E.4 | Principal exclusion criteria |
-Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; < to the equivalent of dexamethasone 40 mg/day for 4 days). -Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study. -Pregnant or lactating women. A serum &#946;-hCG pregnancy test must be performed at the Screening visit, for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilised women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy); -Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for &#8805; 3 years. Exceptions include the following: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancer (TNM stage of T1a or T1b) -Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the latest 12 months. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Confronto tra 2 differenti trattamenti |
|
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |