Primacy Immune Thrombocytopenia
Conditions
Keywords
Primacy immune thrombocytopenia, Adults, Eltrombopag, Long-term remission
Brief summary
A clinical study to evaluate the efficacy of a drug called eltrombopag in adult patients affected of primary immune thrombocytopenia as first treatment to address the disease.
Detailed description
This is a prospective, multicenter phase II trial designed to evaluate the activity of Eltrombopag second line treatment in adult patients with primary Immune Thrombocytopenia (ITP) not responsive or in relapse after a full first line steroids treatment (prednisone or dexamethasone) ± Intravenous Immune Globulin (IVIG).
Interventions
DRUGEltrombopag
Eltrombopag 50 mg/daily.
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of primary ITP; 2. Age ≥ 18 years; 3. Patients are in the new diagnosis or persistent phase of disease (i.e. within month 12 from diagnosis); 4. Patients not responsive or in relapse after a full course of steroid therapy (prednisone 1 mg/kg/d for at least 28 days or 3 cycles of dexamethasone 40 mg/day for consecutive 4 days, according to the GIMEMA ITP0207 trial) ± IVIG; 5. Patients have a platelet count \< 10 x 109/L documented in a single blood cell count; 6. Patients have bleeding symptoms and a platelet count \> 10 \< 30 x 109/L documented in a single blood cell count; 7. Patients have no bleeding symptoms and a platelet count \>10 \< 30 x 109/L in at least 2 blood cell counts at 3 days interval in the week preceding the enrollment with the last count at the day of enrollment; 8. Patients have corticosteroids or IVIG dependence (the need for ongoing or repeated doses administration of corticosteroids or IVIG to maintain a platelet count ≥ 30 x 109/L and/or to avoid bleeding; 9. Written informed consent obtained from the subject; 10. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of enrollment until 6 months after the last dose of study treatment; 11. Female subjects of non-childbearing potential may be enrolled in the study; for this study population, non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause; OR 12. Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 days prior to start of Eltrombopag, has a negative pregnancy test within 14 days of first dose of Eltrombopag, and has agreed to continue adequate contraception during the entire treatment period and for 6 months after completion of the treatment.
Exclusion criteria
1. Diagnosis of secondary ITP. As far as patients with immune thrombocytopenia and antiphospholipid antibodies positivity, individuals without a previous thromboembolic event are excluded only if lupus anticoagulant (LAC) is associated with the presence of anticardiolipin (aCL) and aβ2-Glycoprotein I (aβ2GPI) antibodies; 2. Previous treatment with other anti-ITP second line therapies (i.e. Rituximab, Azathioprine, Cyclosporin-A or other); only patients with a previous full course of steroid (see inclusion criteria for definition) ± IVIG are admitted to the study; 3. Previous treatment with any TPO-R agonists; 4. Patients have life threatening bleeding complications; 5. Patients had deep venous thrombosis (DVT) or arterial thrombosis in the 3 months preceding the enrollment; 6. Patients are HIV, HCV, HBsAg positive; 7. Patients with hepatic impairment (i.e. mild, moderate or severe hepatic impairment (Child-Pugh score \> 6); 8. Patients have a well established liver disease that represents a contraindication for the use of Eltrombopag; 9. Patients are unable to respect the 4-hour interval between Eltrombopag and other medications (e.g. antacids), calcium-rich foods (e.g. dairy products and calcium fortified juices), or supplements containing polyvalent cations such as iron, calcium, aluminium, magnesium, selenium, and zinc; 10. Patients are unable to stop medications that are known to cause a drug-drug interaction with Eltrombopag; 11. Subjects meeting any of the following criteria must not be enrolled in an Eltrombopag study: * Lactating female. * History of another malignancy. Exception: subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures. * Hormone replacement therapy. Subjects must discontinue hormone replacement therapy prior to study enrollment due to the potential for inhibition of Cytochrome P450 (CYP) enzymes that metabolize estrogens and progestins. * Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment. * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Eltrombopag or excipients that contraindicate their participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects who achieve long-term response (6 months sustained response) and able to taper down the dose. | After one year from study treatment. | A patient will achieve this endpoint if at the end of the period of treatment he/she reaches to discontinue Eltrombopag and if, after discontinuation, has absence of bleeding and maintains a platelet count ≥ 30 x 109/L and at least a 2-fold increase from the baseline count in blood cell count performed in the 6 months of the period observation, during which no steroid, Eltrombopag, other anti TPO-R agonists and other anti-ITP medications are administered. |
Secondary
| Measure | Time frame |
|---|---|
| Number of months of response from eltrombopag discontinuation to the last follow-up. | After one year from study treatment. |
| Number of months of complete response from eltrombopag discontinuation to the last follow-up. | After one year from study treatment. |
| Number of bleeding events. | After one year from study treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Modification of immunological parameters during treatment and their relationship with clinical outcomes. (Composite outcome) | At baseline, week 24, 36 and 52 | This study will be performed and completed in all patients enrolled into the study (responders and no-responders). The following biological markers will be evaluated from peripheral blood at baseline, week 24, 36 and 52: 1. Cytokine serum levels; 2. Lymphocyte subpopulations; 3. Cytokine production by T cells ex vivo; 4. Cytokine production by myeloid dendritic cells. |
| Analysis of the relationship between baseline TPO serum level and response to therapy. | After six months from treatment start. | — |
Countries
Italy
Outcome results
None listed