Thalidomide at Low Dose for the Treatment of Patient With Myelodysplastic Syndromes - THAL-SMD-200

Thalidomide for the Treatment of Cytopenias of Patients With Low Risk Myelodysplastic Syndromes

The GFM previously conducted a dose-escalating phase II trial of thalidomide in MDS with a minimum dose of 200mg/d and a maximum dose 800mg/d. Responses were evaluated according to IWG criteria at week 16 and thalidomide continued up to week 56 in responders. 82% patients received at least 8 weeks of treatment and were evaluable. 59% had hematological improvement, mainly on the erythroid lineage (Increase of Hemoglobin). Most responses were observed at low doses and between 4 and 8 weeks.

The objectives of this trial (Thal-SMD-20) are to evaluate the efficacy and tolerance of lower doses thalidomide in low risk MDS patients with transfusion-dependant anemia.

Thalidomide:

First part of the trial: 82 patients at 200mg/day given at bedtime x 12 weeks, decreased to 100mg/day if grade 1 or 2 side. Stopped temporally for 1 week if grade 3 or 4 side effects. Then reintroduced at the same dose. If side effects again, definitively stopped.

Responses evaluated at 12 weeks according to IWG criteria for the erythroid lineage

At week 12:

• If no Hematological improvement (HI): increased to 300mg/day for 8 weeks and then eventually to 400mg/day for 8 weeks more, if no HI.
• If Hematological improvement (HI): continued at the same dose.

Second part of the trial: 30 patients treated at 50mg/day x 12 weeks. Responses evaluated at 12 weeks according to IWG criteria for the erythroid lineage

At week 12:

• If no Hematological improvement (HI): increased to 100mg/day for 8 weeks and then eventually to 200mg/day for 8 weeks more, if no HI.
• If Hematological improvement (HI): continued at the same dose.

Inclusion Criteria:

• Patients ≥18 years, with IPSS Low or Int-1 MDS
• Transfusion dependant anemia above 2 packed red blood cells (PRBC)/month
• ECOG index = 0, 1, 2
• No peripheral neurological disease

Exclusion Criteria:

• MDS patients with IPSS Int-2 or High
• Patients with less than 2 packed red blood cells (PRBC)/month
• Patients with previous history of venous thrombosis
• Patient treated with EPO +/- G-CSF in the 2 months before inclusion in the protocol
• Patient having received intensive chemotherapy in the 3 months before inclusion in the protocol
• Patient having received Thalidomide in a previous protocol
• Patient presenting an iron, B12 vitamin or folic acid uncorrected deficiency
• Patient with peripheral neurological disease
• Patient not being able to subject itself to a regular clinical and biological follow-up
• Pregnant patient or patient in a period of lactation
• Patient refusing to take a contraceptive treatment through out all the study
• Patient receiving drugs able to interfere with the mechanism of action of Thalidomide
• Patient refusing to sign the informed consent.