Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
18 Years
N/A
Both
Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma
Trial Information
Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
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.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome 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.
Outcome Time Frame:
6 months of treatment for each patient
Safety Issue:
No
Principal Investigator
Carlo Visco, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Department of Hematology, San Bortolo Hospital, Vicenza, Italy
Authority:
Italy: The Italian Medicines Agency
Study ID:
VI-Plt-01
NCT ID:
NCT01610180
Start Date:
June 2012
Completion Date:
June 2015
Related Keywords:
- Purpura, Thrombocytopenic, Idiopathic
- Autoimmune Thrombocytopenic Purpura
- Autoimmune Thrombocytopenia
- Chronic Lymphocytic Leukemia
- Non Hodgkin's Lymphoma
- Eltrombopag
- ITP
- LPD
- leukemia
- Immune ThrombocytoPenia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoproliferative Disorders
- Purpura
- Purpura, Thrombocytopenic
- Thrombocytopenia
- Purpura, Thrombocytopenic, Idiopathic
Name | Location |
|---|
