Clinical trial NCT01610180: Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
Official title: Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Purpura, Thrombocytopenic, Idiopathic
Autoimmune Thrombocytopenic Purpura
Autoimmune Thrombocytopenia
Chronic Lymphocytic Leukemia
Non Hodgkin's Lymphoma
Keywords: Eltrombopag
ITP
LPD
leukemia
Immune ThrombocytoPenia
Lead sponsor: Fondazione Progetto Ematologia
Sponsor class: OTHER
First posted: 2012-06-01
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of any of the following B-cell chronic LPD, as defined by WHO 2008 classification: small lymphocytic lymphoma/chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, Hodgkin's lymphoma.
2. Occurrence of ITP diagnosed on the basis of predefined criteria.
3. Not likely to necessitate any cytotoxic treatment for the following 6 months, according to clinical stage and performance status.
4. Platelet count less than 30,000/µL; patients with platelet count between 30 and 50,000/µL only in case of bleeding signs or symptoms.
5. Age greater than or equal to 18 years.
6. Absence of a personal or family (up to first degree relatives) history of venous or arterial thromboembolism.
7. ECOG performance status ≤2.
8. Adequate liver and renal function.
9. Absence of active Hepatitis B (HBsAg+ or HBV-DNA+), Hepatitis C (HCV-Ab+), or HIV infection.

9) Provided informed consent. 10) Negative pregnancy test or lactation 11) No antiplatelet or anticoagulant ongoing treatments

Exclusion Criteria:

1. Subjects with any clinically relevant abnormality, other than LPD or ITP, or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study.
2. Subjects with any concurrent malignant disease other that the LPD and/or a recent history of cancer treatment with systemic chemotherapy and/or radiotherapy. Exception: Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
3. Subjects with screening bone marrow fibers of either MF Grade 3 using European Consensus scale or Grade 4 using Bauermeister scale (see Appendix 1).
4. Subjects with a QTc \>450 msec or \> 480 msec for subjects with Bundle Branch Block.
5. Subjects with recent history of alcohol/drug abuse as determined by the investigator.

Primary outcomes:
measure: 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.
timeFrame: 6 months of treatment for each patient
Secondary outcomes:
measure: Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria.
timeFrame: 9 months
measure: Number of patients meeting permanent discontinuation criteria
timeFrame: From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment)
Other outcomes:
Locations:
city: Vicenza
country: Italy
facility: Department of Hematology, Ospedale San Bortolo
Study officials:
affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy
name: Carlo Visco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.