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

NCT01610180 | Completed Phase 2 DMC

• 1 other identifier: VI-Plt-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Purpura, Thrombocytopenic, Idiopathic; Autoimmune Thrombocytopenic Purpura; Autoimmune Thrombocytopenia; Chronic Lymphocytic Leukemia; Non Hodgkin's Lymphoma

Keywords

Eltrombopag; ITP; LPD; leukemia; Immune ThrombocytoPenia

Outcome Measures

Primary Outcomes (1)

• 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).

  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.

  9 months

• Number of patients meeting permanent discontinuation criteria

  From enrollment to end of study duration (24 weeks) and of extension phase (up to 5 years after first patient enrollment)

Study Arms (1)

Eltrombopag Olamine

OTHER

Eltrombopag Olamine Initial dose 50 mg/day for 14 days. Then adjusted according to platelet count

Drug: Eltrombopag Olamine

Interventions

Eltrombopag Olamine DRUG

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.

Also known as: Revolade, Eltrombopag

Eltrombopag Olamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \) Provided informed consent. 10) Negative pregnancy test or lactation 11) No antiplatelet or anticoagulant ongoing treatments

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Progetto Ematologia: lead

Study Sites (1)

Department of Hematology, Ospedale San Bortolo

Vicenza, 36100, Italy

Location

Related Publications (4)

• 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.

  PMID: 19932433 BACKGROUND

• 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.

  PMID: 17986663 BACKGROUND

• 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.

  PMID: 22322667 BACKGROUND

• 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.

  PMID: 31570488 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Leukemia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chronic Disease; Disease Attributes; Lymphoma

Study Officials

• Carlo Visco, MD

  Department of Hematology, San Bortolo Hospital, Vicenza, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 1, 2012
• Study Start: June 1, 2012
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: July 16, 2018

Record last verified: 2018-07

Locations

IT (1)