Efficacy of Thalidomide in the Treatment of Hereditary Hemorrhagic Telangiectasia (THALI-HHT)
Hereditary Hemorrhagic Telangiectasia, Epistaxis
About this trial
This is an interventional treatment trial for Hereditary Hemorrhagic Telangiectasia focused on measuring Hereditary hemorrhagic telangiectasia, Epistaxis, Thalidomide
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of HHT, according to the diagnostic criteria world-wide recognized (Curacao criteria), with severe recurrent epistaxis (grade 2-3 according to the criteria proposed by Pagella et al., i.e. at least one episode of overt bleeding/week requiring at least one blood transfusion during the last three months), and refractory to mini-invasive surgical procedures, i.e. argon plasma coagulation. For these patients, there is no effective treatment option currently available
- Age > 18 years
- Ability of signing written informed consent
- Women of childbearing potential:
- declared intention not to start a pregnancy throughout the study and for four weeks following the date of the last dose of thalidomide (safe contraception, see Celgene guidelines, "Programma di Prevenzione della Gravidanza")
- negative serum pregnancy test obtained within 48 hours prior to the first dose of Thalidomide
- declared intention to undergo pregnancy tests periodically while on the study medication
- Males with female partner of childbearing potential:
- declared intention not to father throughout the study and for one week following the date of the last dose of thalidomide (safe contraception, see Celgene guidelines, "Programma di Prevenzione della Gravidanza")
- Estimated life expectancy must be greater than 10 months
Exclusion Criteria:
- Pregnant or lactating women, or potentially fertile (both males and females) who have not agreed to avoid pregnancy during the trial period and for four weeks (females) or one week (males) following the date of the last dose of thalidomide
- Neurological diseases
- Psychiatric illness that would prevent granting of informed consent
- Active cardiovascular disease
- High risk for thromboembolic events (comorbidities, such as diabetes or uncontrolled infections, malignancy, immobility, prior history of thromboembolic events, use of erythropoietic agents or other agents such as hormone replacement therapy, central venous catheter, anti-cardiolipin, or anti-beta2 glycoprotein antibodies)
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption since thalidomide capsules contain lactose
Sites / Locations
- Clinica Medica 3, Fondazione IRCCS Policlinico S. Matteo
Arms of the Study
Arm 1
Experimental
Thalidomide
Single arm study: Eligible patients will receive thalidomide at a starting dose of 50 mg/day by mouth at bedtime for 4 weeks. In the event of unsatisfactory/no response, thalidomide dosage will be progressively increased by 50 mg/day every 4 weeks until complete or partial response, to a maximum dose of 200 mg/day. Treatment will be continued until one of the following criteria is met: 8 additional weeks of treatment after the achievement of complete response 16 additional weeks of treatment after the achievement of partial response 24 weeks of treatment completed without response unacceptable toxicity. Then, patients will be followed off of thalidomide for 24 weeks.