Eltrombopag in Second Line Adult Primary Immune Thrombosytopenia
- Registration Number
- NCT02402998
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
- Diagnosis of primary ITP;
- Age ≥ 18 years;
- Patients are in the new diagnosis or persistent phase of disease (i.e. within month 12 from diagnosis);
- 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;
- Patients have a platelet count < 10 x 109/L documented in a single blood cell count;
- Patients have bleeding symptoms and a platelet count > 10 < 30 x 109/L documented in a single blood cell count;
- 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;
- 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;
- Written informed consent obtained from the subject;
- 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;
- 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
- 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.
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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;
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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;
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Previous treatment with any TPO-R agonists;
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Patients have life threatening bleeding complications;
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Patients had deep venous thrombosis (DVT) or arterial thrombosis in the 3 months preceding the enrollment;
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Patients are HIV, HCV, HBsAg positive;
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Patients with hepatic impairment (i.e. mild, moderate or severe hepatic impairment (Child-Pugh score > 6);
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Patients have a well established liver disease that represents a contraindication for the use of Eltrombopag;
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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;
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Patients are unable to stop medications that are known to cause a drug-drug interaction with Eltrombopag;
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eltrombopag Eltrombopag Eltrombopag 50 mg/daily.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Number of bleeding events. After one year from study treatment. 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.
Trial Locations
- Locations (14)
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano
🇮🇹Milano, Italy
Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano
🇮🇹Milano, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
🇮🇹Roma, Italy
AO di Padova Università degli Studi Padova Dipartimento di Medicina Clinica Medica I - Medicina Interna CLOPD
🇮🇹Padova, Italy
Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi
🇮🇹Verona, Italy
Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliera "S.Gerardo"
🇮🇹Monza, Italy
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
🇮🇹Novara, Italy
Azienda Ospedale S. Luigi at University of Torino
🇮🇹Orbassano, Italy
Ospedale "Infermi"
🇮🇹Rimini, Italy
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
🇮🇹Napoli, Italy
Ospedale San Bortolo
🇮🇹Vicenza, Italy
Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine
🇮🇹Udine, Italy