| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed refractory multiple myeloma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10028228 |
|
| 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 |
| The primary objective is to compare the time to progression TTP of three daily doses of thalidomide 100, 200 and 400 mg with high-dose dexamethasone in relapsed refractory multiple myeloma MM patients and to subsequently select the optimum thalidomide dose in terms of median TTP and toxicity. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives The important secondary objectives are to compare each dose of thalidomide with high-dose dexamethasone for the following outcomes response rate; clinical benefit; survival overall and progression free ; quality of life.TTP in the subgroups defined by the number of therapeutic lines before randomisation 1 line versus more than 1 line .The safety of thalidomide compared to dexamethasone will also be evaluated |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| Patients must meet all of the following inclusion criteria to be eligible for enrolment into the study Male or female patients, aged 8805; 18 years at the time of signing the informed consent form; Patients who have been previously diagnosed with MM, who have received between 1 and 3 prior lines of treatment for their disease and who require therapy because of disease progression; Secretory MM with measurable levels of monoclonal protein in serum 10 g/L of IgG M-protein and 5 g/L of IgA M-protein or urine 8805; 200 mg/24hours ; Eastern Cooperative Oncology Group ECOG performance status of 0, 1, or 2; Life expectancy 3 months; Able to adhere to the study visit schedule and other protocol requirements; 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 therapy, during the Treatment Period and for 4 weeks after the last dose, Males must agree to use barrier contraception latex condoms when engaging in reproductive activity during the Treatment Period and for 4 weeks after the last dose. Written, informed consent |
|
| E.4 | Principal exclusion criteria |
| The presence of any of the following will exclude a patient from study enrolment and randomisation Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the Informed Consent Form ICF ; 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 ; Non-secretory multiple myeloma; Any of the following laboratory abnormalities Absolute neutrophil count ANC 500 cells/mm3 0.5 x 109/L ; Platelet count 30,000/mm3 30.0 x 109/L without transfusion support within 7 days before the test; Serum creatinine 3.0 mg/dL 265 mol/L ; Serum aspartate aminotransferase ASAT or alanine aminotransferase ALAT 3.0 x upper limit of normal ULN ; Serum total bilirubin 2.0 mg/dL 34 mol/L ; Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study; Severe cardiac dysfunction according to the New York Heart Association NYHA classification III-IV see Appendix 6 ; Severe bradycardia 50bpm Peripheral neuropathy 8805; Grade 2 NCI CTC V 3.0 in severity; Prior history of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the patient has been free of disease for 8805; 5 years; Patient received any chemotherapy, corticosteroids 10 mg/day prednisone or equivalent or radiation therapy within 4 weeks before randomisation; Previously treated with thalidomide or thalidomide derivatives; Patients refractory to high-dose dexamethasone defined as experiencing less than a PR to dexamethosone, or PD within 6 months after discontinuing dexamethasone, or discontinued dexamethasone because of 8805; Grade 3 dexamethasone-related toxicity. Previous high-dose dexamethasone therapy is defined as 500 mg dexamethasone or equivalent over a 10-week period, whether administered alone or as part of the VAD regimen ; Contraindications for high-dose dexamethasone; Active or chronic gastrointestinal ulcers, active viral infections herpes, varicella, HIV, hepatitis B, hepatitis C , glaucoma, uncontrolled hypertension, or diabetes mellitus, unless well controlled and under strict supervision during dexamethasone treatment; Patient currently enrolled in another clinical trial or who have participated in another trial within the last 4 weeks before randomisation |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to progression time from randomisation to the first documentation of PD, according to the European Bone Marrow Transplantation Group EBMT criteria as determined by the IRC. |
|
| 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) | 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.8.3 |
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 | Yes |
| 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 | 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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