Purpura, Thrombocytopenic, IdiopathicPhase 2NCT01610180
Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
A Phase 2 study testing Eltrombopag Olamine in people with Purpura, Thrombocytopenic, Idiopathic and Autoimmune Thrombocytopenic Purpura, run by Fondazione Progetto Ematologia at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia
- What is being tested?
- Eltrombopag Olamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2012to 30 Jun 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
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.
Read the 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.
- Conditions
- Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma
- Being tested
- Eltrombopag Olamine
- Keywords
- Eltrombopag, ITP, LPD, leukemia, Immune ThrombocytoPenia
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eltrombopag OlamineDrug
Also called Revolade, Eltrombopag
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.
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag Olamine | Other | Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count Receives: Drug: Eltrombopag Olamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months of treatment for each patient
Secondary outcomes (2)
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.
Measured: 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 %.
Measured: From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2012 (estimated)
- Study startJun 2012
- Primary completion30 Jun 2018
- Study completion30 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Purpura, Thrombocytopenic, IdiopathicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Progetto Ematologia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carlo Visco, MD, Principal investigator, Department of Hematology, San Bortolo Hospital, Vicenza, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610180
- Sponsor's protocol ID
- VI-Plt-01
- Status last verified
- Jul 2018
- First submitted
- 30 May 2012
- Last updated
- 16 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19932433Visco 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.
PubMed 17986663Visco 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.
PubMed 22322667Visco 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.
PubMed 31570488
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)
- ClinicalTrials.gov ID
- NCT01610180
- Acronym / sponsor ID
- VI-Plt-01
- Conditions
- Purpura, Thrombocytopenic, Idiopathic, Autoimmune Thrombocytopenic Purpura, Autoimmune Thrombocytopenia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma
- Keywords
- Eltrombopag, ITP, LPD, leukemia, Immune ThrombocytoPenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Fondazione Progetto EmatologiaUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 30 Jun 2018 (actual)
- First posted
- 1 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag Olamine | Other | Drug: Eltrombopag OlamineEltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eltrombopag OlamineAlso: Revolade, EltrombopagInitial dose : 50 mg/day for 14 days. Next doses: 1. 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). 2. If platelet count >60000/µL and ≤200000/µL same dose for the next 14 days. 3. 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. 4. 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. | Drug | Eltrombopag Olamine |
Primary outcome
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.
Time frame: 6 months of treatment for each patient
Response criteria according to the International Working Group publication (Rodeghiero et al, Blood 2009).
2 secondary outcomes
Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria.
Time frame: 9 months
Number of patients meeting permanent discontinuation criteria
Time frame: From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2018.
- Background: PubMed 19932433Visco 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.
- Background: PubMed 17986663Visco 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.
- Background: PubMed 22322667Visco 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.
- Derived from this study: PubMed 31570488Visco 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlo Visco, MD principal investigator
Department of Hematology, San Bortolo Hospital, Vicenza, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag Olamine in people with Purpura, Thrombocytopenic, Idiopathic and Autoimmune Thrombocytopenic Purpura, run by Fondazione Progetto Ematologia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: 6 months of treatment for each patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01610180, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2018.