E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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 |
Phase 1 Primary objective - To determine the maximum tolerated dose (MTD) and recommended phase 2 dose level (RDL) of lenalidomide administered during 21 days of a 4 week cycle, combined with continuous cyclophosphamide and prednisone.
Phase 2 pimary objective - To investigate the efficacy of lenalidomide administered during 21 days of a 4 week cycle, combined with continuous cyclophosphamide and prednisone at the RDL, as determined by the (s)CR+VGPR+PR rate.
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E.2.2 | Secondary objectives of the trial |
Phase 1 Secondary objective - To evaluate toxicity.
Phase 2 Secondary objectives - To evaluate toxicity. - To evaluate progression-free survival - To evaluate overall survival - To evaluate prognostic factors for response and survival - To evaluate the immunomodulatory effects of lenalidomide by using flow cytometric and cytokine analysis
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Multiple myeloma/Salmon & Durie stage II/III A or B • Previous lenaliomide- refractory disease (refractory to prior treatment indicates progressive disease on last prior therapy, best response of stable disease (not CR, VGPR, PR or PD) to last prior therapy, or progressive disease within 3 months (International Uniform Response Criteria for Multiple Myeloma)) is required in both the phase 1 and 2 part of the study1 • 1 previous line of treatment • Age 18 years • WHO performance 0, 1, 2, or 3 • Measurable disease i.e. serum M-protein (>10 g/l), or urinary light-chain excretion (>200 mg/24 h), or proven plasmacytoma by biopsy • Life expectancy at least 3 months • Written informed consent • Patient commits to pregnancy prevention program (for detailed information see section 10.1) •Negative pregnancy tests before inclusion if female of child baring potential; Sexually active women of child bearing potential must agree to use 2 reliable forms of adequate contraception while on study drug (and 4 weeks before and after study drug) (for detailed information see section 10.1) Men must agree not to father a child and to use a condom if his partner is of childbearing potential 1) A therapy-free interval or other lines of therapy between prior lenalidomide therapy and REP is allowed
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E.4 | Principal exclusion criteria |
• Non-secretory myeloma • Known hypersensitivity to lenalidomide • Inadequate marrow reserve as defined by a platelet count <100 x 109/L or an absolute neutrophil count <1.5 x 109/L • Systemic AL amyloidosis • Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrythmias; clinically significant pericardial disease) • Significant hepatic dysfunction (total bilirubin 3 times normal value or transaminases 3 times normal value), unless related to myeloma • Creatinine clearance <30 mL/min • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.) • 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 • Unable or unwillingness to comply with the pregnancy prevention program (for detailed information see section 10.1) • Not able and/or willing to use adequate contraception • Pregnant or lactating females
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 Primary endpoint - Dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RDL) of lenalidomide, cyclophosphamide, combined with prednisone (REP).
Secondary endpoints - Toxicity, especially myelosuppression, polyneuropathy and thrombosis
Phase 2 Primary endpoint - Overall response rate. In this analysis we will consider the best response obtained during treatment
Secondary endpoints - Toxicity, especially myelosuppression, polyneuropathy and thrombosis - Progression free survival (PFS; i.e. time from registration to progression or death from any cause, whichever comes first - Overall survival measured from registration. Patients still alive or lost to follow up are censored at the date they were last known to be alive - Prognostic factors for response and survival - Immunomodulatory effects of lenalidomide by evaluation of T cell subsets and cytokine analysis
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | 8 |
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 | 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
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1 year after last treatment visit of last patient |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 1 |