Clinical trial NCT00455910: Thalidomide at Low Dose for the Treatment of Patient With Myelodysplastic Syndromes - THAL-SMD-200
Official title: Thalidomide for the Treatment of Cytopenias of Patients With Low Risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: Low risk myelodysplastic syndromes
MDS
Bone marrow diseases
Thalidomide
Cytopenias
Anemia
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
First posted: 2007-04-04
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy evaluated at week 12 according to the IWG criterias
Secondary outcomes:
measure: Safety
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Avignon
country: France
facility: CH d'Avignon
city: Bayonne
country: France
facility: CH de la Cote Basque
city: Bobigny
country: France
facility: Hopital Avicenne
city: Brest
country: France
facility: CHU de Brest - Hopital Morvan
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Albert Michallon
city: Lille
country: France
facility: CHRU de Lille - Hopital C. Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice - Hopital de l'Archet 1
city: Paris
country: France
facility: Hotel Dieu
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Necker
city: Perpignan
country: France
facility: CH Joffre
city: Rouen
country: France
facility: Centre Henry Becquerel
city: Toulouse
country: France
facility: CHU Purpan
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy-Brabois
Study officials:
affiliation: Groupe Francophone des Myelodysplasies
name: Didier Bouscary, MD, Ph-D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bouscary D, Legros L, Tulliez M, Dubois S, Mahe B, Beyne-Rauzy O, Quarre MC, Vassilief D, Varet B, Aouba A, Gardembas M, Giraudier S, Guerci A, Rousselot P, Gaillard F, Moreau A, Rousselet MC, Ifrah N, Fenaux P, Dreyfus F; Groupe Francais des Myelodysplasies (GFM). A non-randomised dose-escalating phase II study of thalidomide for the treatment of patients with low-risk myelodysplastic syndromes: the Thal-SMD-2000 trial of the Groupe Francais des Myelodysplasies. Br J Haematol. 2005 Dec;131(5):609-18. doi: 10.1111/j.1365-2141.2005.05817.x.