Primacy Immune Thrombocytopenia Clinical Trial
Official title:
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
| Verified date | August 2021 |
| Source | Gruppo Italiano Malattie EMatologiche dell'Adulto |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 55 |
| Est. completion date | August 28, 2019 |
| Est. primary completion date | May 22, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 aß2-Glycoprotein I (aß2GPI) 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. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi | Bologna | |
| Italy | 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 | Azienda Ospedaliera "S.Gerardo" | Monza | |
| Italy | Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" | Napoli | |
| 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 | AO di Padova Università degli Studi Padova Dipartimento di Medicina Clinica Medica I - Medicina Interna CLOPD | Padova | |
| Italy | Ospedale "Infermi" | Rimini | |
| Italy | Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia | Roma | |
| Italy | Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore | Rome | |
| Italy | Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine | Udine | |
| Italy | Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi | Verona | |
| Italy | Ospedale San Bortolo | Vicenza |
| Lead Sponsor | Collaborator |
|---|---|
| Gruppo Italiano Malattie EMatologiche dell'Adulto |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Modification of immunological parameters during treatment and their relationship with clinical outcomes. (Composite outcome) | 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:
Cytokine serum levels; Lymphocyte subpopulations; Cytokine production by T cells ex vivo; Cytokine production by myeloid dendritic cells. |
At baseline, week 24, 36 and 52 | |
| Other | Analysis of the relationship between baseline TPO serum level and response to therapy. | After six months from treatment start. | ||
| Primary | Number of subjects who achieve long-term response (6 months sustained response) and able to taper down the dose. | 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. | After one year from study treatment. | |
| Secondary | Number of months of response from eltrombopag discontinuation to the last follow-up. | After one year from study treatment. | ||
| Secondary | Number of months of complete response from eltrombopag discontinuation to the last follow-up. | After one year from study treatment. | ||
| Secondary | Number of bleeding events. | After one year from study treatment. |