Association of FcγRIIIA Polymorphism and THPO Expression With Response to Eltrombopag in Refractory ITP Patients

NCT02877212 | Unknown Phase 3 DMC

• 1 other identifier: AFBMTC_ITP_2016
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction. The complex pathogenesis of ITP with multiple challenges to immune system in terms of genetic predisposition, infection, responsiveness to immunosuppressive therapy (IST) and inhibition of platelet production has proven the diversity of constraints in diagnosing and treating ITP. Thrombopoietin receptor agonist (Eltrombopag) is specifically indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This clinical trial aims to investigate the association of Fc gammaRIIIA gene (V158F) genetic predisposition with treatment outcome of Immune Thrombocytopenia (ITP) in refractory ITP patients and especially with Eltrombopag.

Conditions

Immune Thrombocytopenic Purpura (ITP)

Keywords

ITP; Eltrombopag; Steroid refractory; Fc Receptor

Outcome Measures

Primary Outcomes (2)

• The overall response rate 4-6 months after treatment defined by a platelet count > 30 x 109/L with at least a two-fold increase from the initial (pre-treatment) count

  6 months after inclusion

• Fc Receptor polymorphism and THPO expression in responders and non-responders

  The inclusion of 75 patients (25 ITP patients treated with Eltrombopag and 50 subjects with ITP treated with other standard IST) would be considered as sufficient to show an association of the FcgammaRIIIA V158F genotypes distribution and THPO expression with the response for the patients treated with Eltrombopag and other IST at different time points; (M0, M3 and M6 )\*\* \*\*M0=pretreatment sample at 0 month; M3=sample after 3 months of treatment; M6= sample after 6 months of treatment.

  6-12 months after inclusion

Secondary Outcomes (1)

• The Thrombopoietin and cytokine expression among the responders and non responders

  6 months

Study Arms (1)

Study subjects

EXPERIMENTAL

Steroid refractory ITP patients will be given Eltrombopag to investigate the association of treatment outcome with Fc Receptor polymorphism and THPO expression in responders and non responders following comparison correlation with ITP patients treated with standard IST as control group

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

Eltrombopag will be given to steroid refractory ITP patients and ITP patients treated with standard Immunosuppressive therapy (IST) will be taken as control.

Also known as: TPO Receptor agonists

Study subjects

Eligibility Criteria

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

You may qualify if:

• Steroid refractory ITP defined according to the recent consensual criteria (Rodeghiero F et al. Blood 2009),
• Informed consent. The control patients will be included as under;
• Age and sex matched controls
• Control ITP group (treated with standard immunosuppressive therapy (IST) as first and second line treatment)

You may not qualify if:

• Secondary ITP
• Other hematological and malignant disorders

Sponsors & Collaborators

• National Institute of Blood and Marrow Transplant (NIBMT), Pakistan: lead
• Novartis: collaborator

Study Sites (1)

Armed Forces Bone Marrow Transplant Centre

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

Related Publications (4)

• Erickson-Miller CL, Delorme E, Tian SS, Hopson CB, Landis AJ, Valoret EI, Sellers TS, Rosen J, Miller SG, Luengo JI, Duffy KJ, Jenkins JM. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-30. doi: 10.1634/stemcells.2008-0366.

  PMID: 19038790 BACKGROUND

• Nimmerjahn F. Immunomodulation of immunothrombocytopenia. Semin Hematol. 2016 Apr;53 Suppl 1:S10-2. doi: 10.1053/j.seminhematol.2016.04.004. Epub 2016 Apr 6.

  PMID: 27312154 BACKGROUND

• Akyol Erikci A, Karagoz B, Bilgi O. Regulatory T Cells in Patients with Idiopathic Thrombocytopenic Purpura. Turk J Haematol. 2016 Jun 5;33(2):153-5. doi: 10.4274/tjh.2015.0335.

  PMID: 27211045 BACKGROUND

• Milosevic I, Slade E, Drysdale H; COMPare project team. Eltrombopag for chronic immune thrombocytopenia. Lancet. 2016 Jan 23;387(10016):336. doi: 10.1016/S0140-6736(16)00107-0. No abstract available.

  PMID: 26842445 BACKGROUND

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

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

Study Officials

• Parvez Ahmed, FCPS, MCPS

  Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan

  PRINCIPAL INVESTIGATOR

• Andleeb Hanif, M.Phil

  andleebhanif123@gmail.com

  STUDY DIRECTOR

Central Study Contacts

Parvez Ahmed, FCPS, MCPS

CONTACT

+92-51-9270076; parvez101@yahoo.com

Andleeb Hanif, M.Phil

CONTACT

+92-51-9270076; andleebhanif123@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: FCPS, MCPS

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: August 24, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: September 1, 2017
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

PA (1)