Multiple myeloma (MM) is a malignant, lymphoproliferative disease of the B-cell system. The incidence is approximately 4 per 100,000 and it is age-dependent, with an increase in incidence of approximately 6 8 per 100,000 between the ages of 70 and 80 years. MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Product Name: Thalidomide Pharmion
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: THALIDOMIDE
CAS Number: 50351
Concentration unit: mg milligram(s)
Concentration type: range
Concentration num
Sponsors
Celgene International Sarl
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrolment and randomisation into the study: · Male or female patients, aged = 18 years at the time of signing the informed consent form; · Patients who have been previously diagnosed with MM (see Appendix 3 for the standard definition of MM), who have received between 1 and 3 prior lines of treatment for their disease (see Appendix 4 for definition of line of treatment), and who require therapy because of disease progression (see Appendix 1 for PD definition); · 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 (= 200 mg/24hours); · ECOG performance status of 0, 1, or 2 (see Appendix 5); · 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 the 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a patient from study enrolment: · 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 ß-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 MM; · Any of the following laboratory abnormalities: - Absolute neutrophil count (ANC) 3.0 mg/dL (265 µmol/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 µmol/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 ( 10 mg/day prednisone or equivalent) 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 dexamethasone, or PD within 6 months after discontinuing dexamethasone, or discontinued dexamethasone because of = 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 enrolled in another clinical trial or who have participated in another trial within the last 4 weeks before randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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. Population pharmacokinetics and pharmacodynamics in thalidomide-treated patients only will be evaluated. ;Primary end point(s): The primary endpoint in this study is the evaluation of IRC-documented time to progression (TTP). The TTP is calculated as the time from randomisation to the first documentation of PD, based on the myeloma response determination EBMT criteria (see Appendix 1). When disease progression is based on increasing monoclonal protein levels it must be confirmed at least once within 1 to 4 weeks after the first determination of disease progression. Thus if the second monoclonal protein measurement confirms disease progression, TTP will be calculated from randomisation to the time of the first monoclonal protein measurement. Disease progression based on bone marrow findings, worsening lytic bone disease, progressively enlarging, extramedullary plasmacytomas, or hypercalcaemia does not require a second confirmatory measurement. | — |
Countries
Czech Republic, Germany, Hungary, Italy, Portugal, United Kingdom
Outcome results
None listed