Patients older than 15 years with hematologic or pulmonary lesions of telomeropathies. MedDRA version: 20.0 Level: PT Classification code 10062759 Term: Congenital dyskeratosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: DANAZOL 200mg
Product Name: DANAZOL 200mg
Product Code: G03XA01
Pharmaceutical Form: Capsule
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient (s): - having a telomeropathy defined by the existence of a constitutional deleterious mutation of a gene involved in the maintenance of telomeres (TERT, TERC, DKC1, TINF2, RTEL1, PARN, ACD, NHP2, NOP10, NAF1, WRAP53, CTC1, ERCC6L2, USB1, POT1, DNAJC21 or a newly identified gene responsible for telomeropathy), - 15 years of age or older, - with severe hematologic involvement (platelets =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patient (s): - with HIV infection or active infection with hepatitis B or hepatitis C, - with severe hepatic impairment: transaminases ASAT and / or ALAT> 5N, or conjugated bilirubinemia> 30? mol / L, TP <50% (except vitamin K deficiency), or splanchnic thrombosis - having a tumoral pathology that has been active or treated for less than 5 years, with the exception of basal cell carcinoma or carcinoma in situ of the cervix, - having a history of organ transplantation or hematopoietic stem cells or having an indication for hematopoietic stem cell transplantation or organ transplantation within 6 months of inclusion, - having an absolute contraindication to treatment with danazol: active thrombosis or history of thromboembolic disease, porphyria, severe renal or cardiac insufficiency (NYHA stage III or IV), androgen-dependent tumor, pathological genital haemorrhage of etiology indeterminate, - having already received danazol for the treatment of telomeropathy, - having received another androgen within a period of less than 6 months, - receiving another experimental treatment, - receiving another hormonal treatment, - receiving treatment with simvastatin - unexplored pathological genital bleeding Concomitant treatment with Simvastatin - having a pregnancy plan and not committing to effective contraception while taking the treatment, - breastfeeding, - under tutorship or curatorship.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main Objective: To evaluate the benefit of danazol at 12 months on the clinical response.;Secondary Objective: ; Primary end point(s): Main Evaluation Criterion: For patients with bone marrow failure, the hematologic response at 12 months depending on the line (s) affected: - 1.5 point increase in hemoglobin (g / dL) - and / or increase of 20 G / L of the platelet count and / or an increase of 0.5 G / L in the neutrophil counts. For patients with pulmonary fibrosis, a decrease of less than 5% in forced vital capacity at 12 months Secondary evaluation criteria: For all patients: - Hepatic tolerance (biological at 1, 2, 3, 6, 9 and 12 months, ultrasound imaging at 6 months and MRI at 12 months), - Systemic tolerance: endocrinology (virilization, weight, blood glucose, LDL, HDL cholesterol and triglycerides) at 3, 6, 9, 12 months, bone (bone events and change in osteodensitometry) at 12 months, muscle (cramps and muscle enzymes) at 3, 6, 9 and 12 months, increase in PSA at 3, 6 and 12 months for men, - Evolution of pulmonary parenchymal abnormalities at CT scan at 6 and 12 months, - Evolution of the telomere length by Flow Fish at 12 months, - appearance of cytological and cytogenetic abnormalities at 12 months (myelogram with karyotype at M12), - Quality of life (EORTC QLQ-C30, v3.0) at 3, 6 and 12 months, - Survival at 3, 6, 9 and 12 months. For patients with bone marrow failure - Haematological response at 3, 6 and 9 months, - Complete haematological response at 3, 6, 9 and 12 months (Hb> 10 g / dL, PNN> 1 G / L and platelets> 100 G / L), - Transfusion independence at 3, 6, 9 and 12 months, - Evolution of forced vital capacity and DLCO | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed