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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Fondazione Progetto Ematologia
Sponsor:
Information provided by (Responsible Party):
Fondazione Progetto Ematologia
ClinicalTrials.gov Identifier:
NCT01610180
First received: May 30, 2012
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic
Autoimmune Thrombocytopenic Purpura
Autoimmune Thrombocytopenia
Chronic Lymphocytic Leukemia
Non Hodgkin's Lymphoma
Drug: Eltrombopag Olamine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label Multicenter Study of Eltrombopag for the Treatment of Immune ThrombocytoPenia (ITP) Secondary to Chronic Lymphoproliferative Disorders (LPDs)

Resource links provided by NLM:


Further study details as provided by Fondazione Progetto Ematologia:

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. [ Time Frame: 6 months of treatment for each patient ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of the safety profile of eltrombopag in patients with LPD using the CTCAE criteria. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 26
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag
Single arm trial
Drug: Eltrombopag Olamine

Subjects will initiate study medication at an oral dose of 50 mg/day (25 mg/day for East Asians and for patients with grade 1 serum liver tests impairment).

Treatment scheme and dose adjustments:

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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610180

Contacts
Contact: Carlo Visco, MD 0444 753626 ext +39 visco@hemato.ven.it
Contact: Francesco Rodeghiero, MD 0444 753626 ext +39 rodeghiero@hemato.ven.it

Locations
Italy
Department of Hematology, Ospedale San Bortolo Recruiting
Vicenza, Italy, 36100
Contact: Carlo Visco, MD       visco@hemato.ven.it   
Principal Investigator: Carlo Visco, MD         
Sponsors and Collaborators
Fondazione Progetto Ematologia
Investigators
Principal Investigator: Carlo Visco, MD Department of Hematology, San Bortolo Hospital, Vicenza, Italy
  More Information

Publications:
Responsible Party: Fondazione Progetto Ematologia
ClinicalTrials.gov Identifier: NCT01610180     History of Changes
Other Study ID Numbers: VI-Plt-01
Study First Received: May 30, 2012
Last Updated: September 25, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Fondazione Progetto Ematologia:
Eltrombopag
ITP
LPD
leukemia
Immune ThrombocytoPenia

Additional relevant MeSH terms:
Thrombocytopenia
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Blood Platelet Disorders
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on July 29, 2014