Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP)

NCT00902018 | Completed Phase 2 Results

• 1 other identifier: 0809009980
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to further evaluate the effects that eltrombopag (and romiplostim) have on platelets in subjects with chronic ITP. Eltrombopag is approved by the Food and Drug Administration (FDA) for the treatment of low platelets in patients with chronic ITP. It is being further studied by GlaxoSmithKline (now Novartis) in other conditions associated with low platelets. This research study is being done because eltrombopag has been shown to increase platelet counts in a different way than other therapies for ITP. The investigators want to further study how eltrombopag and romiplostim affect subjects and their platelets to determine how the study drug should best be used in ITP treatment.

Conditions

Immune Thrombocytopenia

Keywords

ITP

Outcome Measures

Primary Outcomes (2)

• Number of Patients for Whom Eltrombopag Increases the Platelet Count to > 50,000/uL

  number of patients in whom Platelet Counts measured on days 8 and 15 after eltrombopag treatment increase to \> 50,000/uL counts on other days are just used to be sure the ones on days 8 and 15 are reasonably accurate and representative

  platelet counts on days 8 and 15

• Number of Patients Who Received Romiplostim and Increased Their Platelet Counts to > 50,000/uL

  number of participants in whom platelet counts measured on day 8 and day 15 after treatment(s) with romiplostim 10 micrograms/kg on days 1 and 8

  platelet counts on days 8 and 15

Secondary Outcomes (1)

• How Many Patients Developed SAEs and/or Abnormal Liver Tests to a Level > 2 Times the Upper Limit of Normal

  on days 8 and 15

Other Outcomes (1)

• Change From Baseline After Eltrombopag Treatment of Platelet Parameters

  testing on days 8 and 15

Study Arms (3)

eltrombopag

EXPERIMENTAL

10 ITP patients were treated with daily oral eltrombopag 75mg for 2 weeks and complete testing was done at weekly intervals 3 times they then were allowed to receive long-term eltrombopag

Drug: Eltrombopag

romiplostim

EXPERIMENTAL

3 of the patients who received eltrombopag were also treated with romiplostim 10 micrograms/kg weekly for 2 weeks with the same complete testing done at weekly intervals three times after a washout period \> 1 month they then resumed long-term eltrombopag

Drug: Romiplostim

healthy controls

SHAM COMPARATOR

no intervention single blood draw with complete studies

Other: healthy controls

Interventions

Eltrombopag DRUG

The 10 subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times, weekly, for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months.

Also known as: revolade, promacta

eltrombopag

Romiplostim DRUG

three of the patients treated with eltrombopag will be treated with weekly romiplostim at a dose of 10 micrograms/kg weekly for 2 weeks with testing at weekly intervals for 3 times

Also known as: amg531, nplate

romiplostim

healthy controls OTHER

single blood draw for all measures included in the intervention arms

Also known as: volunteers not receiving any treatment

healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has signed and dated a written informed consent
• Male or female adults (≥18 years) diagnosed with either primary ITP according to the American Society for Hematology or British Committee for Standards in Haematology (ASH/BCSH) guidelines \[Blood, 1996; British Journal of Haematology, 2003\] for at least three months prior to study entry or with ITP secondary to Evans syndrome, systemic lupus erythematosus (SLE), or Common Variable Immunodeficiency (including hypogammaglobulinemia).
• Subjects must have responded with a platelet count \> 30,000/µL to a previous ITP therapy including thrombopoietic agents.
• Platelet count \< 30,000/µL
• Female subjects of childbearing potential are practicing an acceptable method of contraception or are completely abstinent from intercourse.

You may not qualify if:

• Active infection
• Previously treated with thrombopoietic agents IF either no response at a therapeutic dose (peak platelet count \< 50k) OR treatment with the agent within the past 4 weeks
• Currently treated with concomitant ITP medication that has not been stable in dose for at least 2 weeks - only prednisone, azathioprin, and danazol are allowed.
• Female subjects who are nursing or pregnant
• Thrombosis of any kind within past 6 months or on blood thinners because of thrombosis.
• Intravenous Immunoglobulin (IVIG), IV anti-D, bolus corticosteroids or vinca alkaloids within the past week
• Other cytotoxic or immunosuppressive ITP therapy within the past 8 weeks or rituximab within the past 12 weeks
• Active non-dermatologic malignancy defined as presence of known tumor ie. visible by radiography or evident on blood or bone marrow testing OR receiving chemotherapy within past 2 months
• Hemoglobin \< 10 gm/dl or white blood cell count \< 2,500/ul
• Liver function tests (ALT, Aspartate Aminotransferase (AST), or total bilirubin) \> three times upper limit of normal (ULN)
• Creatinine \> two times upper limit of normal (ULN)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (1)

• Mitchell WB, Pinheiro MP, Boulad N, Kaplan D, Edison MN, Psaila B, Karpoff M, White MJ, Josefsson EC, Kile BT, Bussel JB. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia. Am J Hematol. 2014 Dec;89(12):E228-34. doi: 10.1002/ajh.23832. Epub 2014 Sep 2.

  PMID: 25132654 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

eltrombopag; romiplostim

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

Results Point of Contact

• Title: Dr James Bussel
• Organization: Weill Cornell Medical College

jbussel@med.cornell.edu

22-746-3474

Study Officials

• James B. Bussel, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 10 patients on eltrombopag and 3 were then treated with romiplostim 10 healthy controls

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 14, 2009
• Study Start: January 1, 2009
• Primary Completion: September 7, 2015
• Study Completion: September 7, 2015
• Last Updated: March 18, 2019
• Results First Posted: March 18, 2019

Record last verified: 2019-03

Locations

US (1)