Eltrombopag in Second Line Adult Primary Immune Thrombosytopenia

Eltrombopag as Second Line Therapy in Adult Patients With Primary Immune Thrombocytopenia (ESTIT Study) in an Attempt to Achieve Long-term Remission: a Single Arm Multicenter Phase II Clinical and Biological Study

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.

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).

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.