Thalidomide 100 mg/Day Versus Thalidomide 400 mg/Day in Relapse Refractory Multiple Myeloma

Multicenter, Randomized Study Comparing the Efficacy and Safety of Two Doses of Thalidomide (100 mg/Day Versus 400 mg/Day) in the Treatment of Subjects With Refractory or Relapsed Multiple Myeloma.

The objective of this study is to show that thalidomide at a dose of 100 mg/d (with remedial treatment with dexamethasone if a progression occurs) is equivalent in terms of efficacy with thalidomide at 400 mg/d (with remedial treatment with dexamethasone if a progression occurs) in the treatment of refractory or relapsed multiple myeloma after at least two courses of treatment. The use of thalidomide at 100 mg/d should reduce the side effects and improve the safety of the treatment.

Inclusion Criteria:

• Patient over 18 years who has been informed about the potential risks and side effects of the treatment and having signed an informed consent to take part in the various aspects of the study.

• Having a refractory or relapsed multiple myeloma after at least two courses of treatment.

• The patients with a refractory or relapsed multiple myeloma after a single course of treatment that included an alkylating drug, can be included if there is no alternative treatment.

• Concerning the thalidomide: Agreement to use and introduction of effective contraception by all the patients:

  1. For women of childbearing potential

     • Oral estroprogestogen contraception introduced at least 1 month before the first administration of thalidomide, and continued until the first menstruation following the end of the treatment, and their partners use a condom.
     • Qualitative serum test for beta-HCG negative: to be done on Day 2 or 3 of the menstrual cycle just before the 1st prescription of thalidomide; in a context of spaniomenorrhea or amenorrhea the test should be done within 3 days after the 1st prescription of thalidomide.

  2. For post-menopausal women

     • 1st situation: Known sterility due to:

       • total hysterectomy;
       • total ovariectomy;
       • total salpingectomy

     • 2nd situation: Natural menopause

       • amenorrhea for at least 1 year and
       • negative progestagen test and
       • plasma FSH > 50 IU/l

  3. For men: Throughout the duration of the treatment and for 3 months after the end of the protocol (i.e. one spermatogenesis cycle), sexual intercourse must always be protected by using a condom.

Exclusion Criteria:

• Pregnant or breast-feeding women or those of childbearing potential who are not using an effective method of contraception or the lack of protection during sexual intercourse in men.
• Patients who have already received treatment with thalidomide.
• Contraindication to thalidomide.
• Patient who has an absolute contraindication to dexamethasone.
• Patient with a history of deep vein thrombosis and who is not taking effective oral anticoagulation (the anticoagulant must be continued throughout the entire study).
• Performance index more than or equal to 3, unless the patient is bedridden as a result of the progress of the myeloma.
• Any situations that do not permit adequate follow-up of the study.