E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Multiple Myeloma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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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 |
Determine whether the association of R-MPT as salvage treatment is safe and effective in patients with advanced myeloma. The safety profile will be assessed by showing - a grade 3 non-hematologic toxicity rate 30 - a grade 4 hematologic toxicity rate 30 Grade 4 neutropenia a week, or any Grade 4 hematologic toxicity except neutropenia The efficacy profile will be assessed by showing - a PR rate 60 - a VGPR rate 40 following the proposed regimen |
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E.2.2 | Secondary objectives of the trial |
Determine the duration of the PFS Determine the duration of the OS Describe the safety and efficacy profile of the R-MPT treatment with two different Thalidomide doses 50 and 100 mg Determine whether responses obtained with R-MPT treatment are associated with a prolongation of PFS, in comparison with that of non-responding patients |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patient is of a legally consenting age as defined by local regulations 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time one highly effective method and one additional effective method Highly Effective Methods Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner s vasectomy; Additional Effective Methods Latex condom; Diaphragm; Cervical Cap for 4 weeks prior to beginning study drug therapy, during study drug therapy including dose interruption and for 4 weeks after discontinuation of lenalidomide therapy. 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. Patient was previously diagnosed with symptomatic multiple myeloma based on standard criteria 12 , and has measurable disease, defined as follows a Secretory myeloma 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; b Non-secretory myeloma 30 plasma cells in the bone marrow and at least one plasmacytoma 2cm as determined by clinical examination or applicable radiographs i.e., MRI or CT scan . Patient is relapsed or refractory after one or two lines Patient has a Karnofsky performance status 8805; 60 Patient has a life-expectancy 3 months Patient has not active infectious hepatitis type B or C, and he has HIV negative test Patient has not 61619;Grade 2 peripheral neuropathy within 14 days before enrollment Patient has not known hypersensitivity to thalidomide Patient has not been previously treated with R-MP or MPT association therapy Patient has the following laboratory values within 14 days before Baseline day 1 of the Cycle 1 Platelet count 8805; 100 x 109/L without transfusion support within 7 days before the test. Absolute neutrophil count ANC 8805; 1.0 x 109/L without the use of growth factors. Corrected serum calcium 8804; 14 mg/dL 3.5 mmol/L . Aspartate transaminase AST 8804; 2.5 x the upper limit of normal ULN . Alanine transaminase ALT 8804; 2.5 x the ULN. Total bilirubin 8804; 1.5 x the ULN. Calculated or measured creatinine clearance 8805; 20 mL/minute |
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E.4 | Principal exclusion criteria |
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2. Pregnant or beast feeding females. 3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 4. Use of any other concomitant standard/experimental anti-myeloma drug or therapy 5. Prior induction therapy with R-MP or M-PT association 6. Any of the following laboratory abnormalities Platelet count 100 x 109/L. Absolute neutrophil count 1.0 x 109/L. Aspartate transaminase AST 2.5 x the upper limit of normal ULN . Alanine transaminase AST 2.5 x the ULN. Total bilirubin 1.5 x the ULN. Corrected serum calcium 14 mg/dL 3.5 mmol/L . Calculated or measured creatinine clearance 20 mL/minute 7. Known positive for HIV or active infectious hepatitis, type B or C. 8. Patient has Grade 2 peripheral neuropathy within 14 days before enrollment. 9. Known hypersensitivity to thalidomide. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Determine whether the association of R-MPT as salvage treatment is safe and effective in patients with advanced myeloma. The safety profile will be assessed by showing - a grade 3 non-hematologic toxicity rate 30 - a grade 4 hematologic toxicity rate 30 Grade 4 neutropenia a week, or any Grade 4 hematologic toxicity except neutropenia The efficacy profile will be assessed by showing - a PR rate 60 - a VGPR rate 40 following the proposed regimen |
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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 | 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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | 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.8.5 | 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 | Information not present in EudraCT |
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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |