Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)

July 12, 2018 updated by: Fondazione Progetto Ematologia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Vicenza, Italy, 36100
        • Department of Hematology, Ospedale San Bortolo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Eltrombopag Olamine
Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count
Drug: Eltrombopag Olamine

Initial 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.
Other Names:
  • Revolade
  • Eltrombopag

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.
Time Frame: 6 months of treatment for each patient
Response criteria according to the International Working Group publication (Rodeghiero et al, Blood 2009).
6 months of treatment for each patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria.
Time Frame: 9 months
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.
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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Progetto Ematologia

Investigators

  • Principal Investigator: Carlo Visco, MD, Department of Hematology, San Bortolo Hospital, Vicenza, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

June 30, 2018

Study Completion (Actual)

June 30, 2018

Study Registration Dates

First Submitted

May 30, 2012

First Submitted That Met QC Criteria

May 31, 2012

First Posted (Estimate)

June 1, 2012

Study Record Updates

Last Update Posted (Actual)

July 16, 2018

Last Update Submitted That Met QC Criteria

July 12, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VI-Plt-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Lymphocytic Leukemia

Clinical Trials on Eltrombopag Olamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe