Back to resultsEltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
Primary Purpose
Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Eltrombopag Olamine
Sponsored by
About this trial
This is an interventional treatment trial for Purpura, Thrombocytopenic, Idiopathic focused on measuring Eltrombopag, ITP, LPD, leukemia, Immune ThrombocytoPenia
Eligibility Criteria
Inclusion Criteria:
- 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.
- Occurrence of ITP diagnosed on the basis of predefined criteria.
- Not likely to necessitate any cytotoxic treatment for the following 6 months, according to clinical stage and performance status.
- 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.
- Age greater than or equal to 18 years.
- Absence of a personal or family (up to first degree relatives) history of venous or arterial thromboembolism.
- ECOG performance status ≤2.
- Adequate liver and renal function.
- 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:
- 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.
- 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.
- Subjects with screening bone marrow fibers of either MF Grade 3 using European Consensus scale or Grade 4 using Bauermeister scale (see Appendix 1).
- Subjects with a QTc >450 msec or > 480 msec for subjects with Bundle Branch Block.
- Subjects with recent history of alcohol/drug abuse as determined by the investigator.
Sites / Locations
- Department of Hematology, Ospedale San Bortolo
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Eltrombopag Olamine
Arm Description
Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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 %.
Full Information
NCT ID
NCT01610180
First Posted
May 30, 2012
Last Updated
July 12, 2018
Sponsor
Fondazione Progetto Ematologia
1. Study Identification
Unique Protocol Identification Number
NCT01610180
Brief Title
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
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
June 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Progetto Ematologia
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma
Keywords
Eltrombopag, ITP, LPD, leukemia, Immune ThrombocytoPenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eltrombopag Olamine
Arm Type
Other
Arm Description
Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count
Intervention Type
Drug
Intervention Name(s)
Eltrombopag Olamine
Other Intervention Name(s)
Revolade, Eltrombopag
Intervention Description
Initial dose : 50 mg/day for 14 days.
Next doses:
If platelet count <60000/µL, increase daily dose by 25 mg to a maximum of 150 mg/day for next 14 days in 14 days courses. If response criteria not met after 14 days of the maximum dose stop treatment (no response).
If platelet count >60000/µL and ≤200000/µL same dose for the next 14 days.
If platelet count >200000/µL and ≤400000/µL decrease the daily dose by 25 mg. Wait 14 days to assess the effects of this and any subsequent dose adjustments.
If platelet count >400000/µL, stop Eltrombopag; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is <150000/µL, reinitiate therapy at a daily dose reduced by 25 mg.
Primary Outcome Measure Information:
Title
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.
Description
Response criteria according to the International Working Group publication (Rodeghiero et al, Blood 2009).
Time Frame
6 months of treatment for each patient
Secondary Outcome Measure Information:
Title
Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria.
Description
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.
Time Frame
9 months
Title
Number of patients meeting permanent discontinuation criteria
Description
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 %.
Time Frame
From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Occurrence of ITP diagnosed on the basis of predefined criteria.
Not likely to necessitate any cytotoxic treatment for the following 6 months, according to clinical stage and performance status.
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.
Age greater than or equal to 18 years.
Absence of a personal or family (up to first degree relatives) history of venous or arterial thromboembolism.
ECOG performance status ≤2.
Adequate liver and renal function.
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:
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.
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.
Subjects with screening bone marrow fibers of either MF Grade 3 using European Consensus scale or Grade 4 using Bauermeister scale (see Appendix 1).
Subjects with a QTc >450 msec or > 480 msec for subjects with Bundle Branch Block.
Subjects with recent history of alcohol/drug abuse as determined by the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlo Visco, MD
Organizational Affiliation
Department of Hematology, San Bortolo Hospital, Vicenza, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology, Ospedale San Bortolo
City
Vicenza
ZIP/Postal Code
36100
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
19932433
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.
Results Reference
background
PubMed Identifier
17986663
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.
Results Reference
background
PubMed Identifier
22322667
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.
Results Reference
background
PubMed Identifier
31570488
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.
Results Reference
derived
Learn more about this trial
Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
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