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With conventional treatments (i.e. iv Ig, steroids) the overall response rate of ITP secondary to LPD is generally lower than in primary ITP, and usually not higher than 50% (95% CI 27-72). Eltrombopag which has proved very effective in primary ITP could be effective also in ITP secondary to LPDs.
This novel ITP specific treatment might spare these patients not only from bleeding risk but also from toxic or inappropriate cytotoxic therapies, not otherwise demanded by the burden of the underlying disease.
The denomination of Chronic Lymphoproliferative Disorders (LPD) encompasses a variety of indolent lymphomas grouped into a single clinical category and, as such, this terminology is not included in the current WHO classification. With indolent lymphomas clinicians refer to those lymphomas not associated with an aggressive clinical course and in which often treatment can be delayed. Specifically the following lymphomas by the WHO classification will be considered among indolent lymphomas: small lymphocytic lymphoma/chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, hairy-cell leukemia, Hodgkin's lymphoma. In 1 to 5% of the different LPDs (lowest in follicular lymphoma, highest in chronic lymphocytic leukemia) a clinically relevant thrombocytopenia, often complicated by bleeding symptoms, may complicate the clinical course, frequently still when the tumor burden is low and not demanding treatment. This thrombocytopenia, when not accompanied by massive bone marrow tumor infiltration or not secondary to chemotherapeutic treatment, is thought to share an immune pathogenic mechanism similar to primary immune thrombocytopenia (ITP).
With conventional treatments (i.e. iv Ig, steroids) the overall response rate of ITP secondary to LPD is generally lower than in primary ITP, and usually not higher than 50% (95% CI 27-72). Therefore, any new treatment having a response rate above 50% but not inferior than 20% could be considered a promising treatment for ITP secondary to LPD. Furthermore, no significant platelet increase is expected without treatment in ITP secondary to LPD. Eltrombopag which has proved very effective in primary ITP could be effective also in ITP secondary to LPDs.
This novel ITP specific treatment might spare these patients not only from bleeding risk but also from toxic or inappropriate cytotoxic therapies, not otherwise demanded by the burden of the underlying disease.
Phase 2, single arm, open-label, prospective, multicenter, safety/efficacy study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eltrombopag Olamine | Other | Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eltrombopag Olamine | Drug | Initial dose : 50 mg/day for 14 days. Next doses:
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of responders to eltrombopag as defined by changes in the platelet count, in platelet transfusion requirements and/or in the bleeding symptoms during the 6 months of treatment. | Response criteria according to the International Working Group publication (Rodeghiero et al, Blood 2009). | 6 months of treatment for each patient |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria. | Adverse event reports graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 and laboratory assessments at each on-treatment and post-treatment visit. Physical examination, general laboratory tests, including liver function tests, blood cell count and peripheral blood smear examination, flow cytometry at scheduled visits. Bone marrow biopsy, CT scan of the neck, chest and abdomen at enrollment, if not already done in the three preceding months, at the end of study and 3 months thereafter. |
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Inclusion Criteria:
9) Provided informed consent. 10) Negative pregnancy test or lactation 11) No antiplatelet or anticoagulant ongoing treatments
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carlo Visco, MD | Department of Hematology, San Bortolo Hospital, Vicenza, Italy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Hematology, Ospedale San Bortolo | Vicenza | 36100 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19932433 | Background | Visco C, Rodeghiero F. Immune thrombocytopenia in lymphoproliferative disorders. Hematol Oncol Clin North Am. 2009 Dec;23(6):1261-74. doi: 10.1016/j.hoc.2009.08.006. | |
| 17986663 | Background | Visco C, Ruggeri M, Laura Evangelista M, Stasi R, Zanotti R, Giaretta I, Ambrosetti A, Madeo D, Pizzolo G, Rodeghiero F. Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia. Blood. 2008 Feb 1;111(3):1110-6. doi: 10.1182/blood-2007-09-111492. Epub 2007 Nov 6. |
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|
|
| 9 months |
| Number of patients meeting permanent discontinuation criteria | The following permanent discontinuation criteria were applied during the study and extension period: failure to respond; progression of the underlying disease demanding treatment; drug related toxicity or any adverse events ≥ grade 3 or peripheral blood and/or bone marrow findings suggesting marrow fibrosis (grade 3 or 4 of Bauermaister scale) or myelodisplasia or myeloproliferation including an increment of CD4 positive cell > 3 %. | From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment) |
| 22322667 | Background | Visco C, Maura F, Tuana G, Agnelli L, Lionetti M, Fabris S, Novella E, Giaretta I, Reda G, Barcellini W, Baldini L, Neri A, Rodeghiero F, Cortelezzi A. Immune thrombocytopenia in patients with chronic lymphocytic leukemia is associated with stereotyped B-cell receptors. Clin Cancer Res. 2012 Apr 1;18(7):1870-8. doi: 10.1158/1078-0432.CCR-11-3019. Epub 2012 Feb 9. |
| 31570488 | Derived | Visco C, Rodeghiero F, Romano A, Valeri F, Merli M, Quaresimini G, Volpetti S, Santi RM, Carli G, Lucchini E, Passamonti F, Rambaldi A, Motta G, Borchiellini A, d'Amore ESG, Ruggeri M. Eltrombopag for immune thrombocytopenia secondary to chronic lymphoproliferative disorders: a phase 2 multicenter study. Blood. 2019 Nov 14;134(20):1708-1711. doi: 10.1182/blood.2019001617. |
| ID | Term |
|---|---|
| D016553 | Purpura, Thrombocytopenic, Idiopathic |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D008223 | Lymphoma |
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| ID | Term |
|---|---|
| C520809 | eltrombopag |
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