Protocol Number: 09-H-0199

Title:

A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R agonist), Eltrombopag, in Patients with Low to Int-2 Risk Myelodysplastic Syndrome (MDS)

Number:

09-H-0199

Summary:

Background:

- Myelodysplastic syndromes (MDS) are bone marrow disorders characterized by anemia, neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet counts). Patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as a risk of progression to acute leukemia. Standard treatments for MDS have significant relapse rates. MDS patients with thrombocytopenia who fail standard therapies require regular, expensive, and inconvenient platelet transfusions, and are at risk for further serious bleeding complications.

- Eltrombopag is a drug designed to mimic the protein thrombopoietin, which causes the body to make more platelets. Eltrombopag has been able to increase platelet counts in healthy volunteers and in patients with chronic ITP (a disease where patients destroy their own platelets very rapidly and thus develop thrombocytopenia), but researchers do not know if the drug can increase platelet counts in patients with MDS.

Objectives:

- To find out whether eltrombopag can improve platelet counts in patients with MDS.

- To determine whether eltrombopag is safe for patients with MDS.

Eligibility:

- Patients 18 years of age and older who have consistently low blood platelet counts related to MDS that has not responded to conventional treatment.

Design:

- Treatment with eltrombopag tablets once per day for 90 days.

- Participants will be monitored closely throughout the initial treatment, with weekly blood tests and separate evaluations at the National Institutes of Health (NIH) treatment center every 4 weeks. Bone marrow biopsies may be conducted to check for abnormalities in bone marrow.

- If patients show signs of improved platelet counts after 90 days, treatment will continue with additional doses of eltrombopag.

- Patients who discontinue taking eltrombopag will be evaluated at the NIH treatment center 4 weeks after ending treatment, and again 6 months after ending treatment to check for potential side effects.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Diagnosis of MDS, with WHO classification of RA, RARS, RCMD-RS, or RCMD with refractory thrombocytopenia.

IPSS risk scores of low, intermediate-1, or intermediate-2.

Platelet count less than or equal to 30,000/ micro L

Age greater than or equal to 18 years old

Off all other treatments for MDS (except stable dosing of filgrastim [G-CSF], erythropoietin, and transfusion support) for at least four weeks. Filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented neutropenia (< 500/UI) as long as they meet the criteria for thrombocytopenia as stated above. Filgrastim (G-CSF) must be held for 3 weeks prior to enrollment bone marrow biopsy and prior to each study assessment bone marrow biopsy.

EXCLUSION CRITERIA:

WHO classification of chronic myelomonocytic leukemia (CMML), RAEB-1, RAEB-2, AML

Paroxysmal nocturnal hemoglobinuria (PNH) clone size in neutrophils of greater than or equal to 50%

Bone marrow reticulin fibrosis of grade 3 or higher

Prior treatment with romiplostim or other TPO-R agonists

Treatment with horse or rabbit ATG or Campath within 6 months of study entry.

Creatinine > 2.5

Bilirubin > 2.0

SGOT or SGPT > 2 times the upper limit of normal

Subjects infected with Hepatitis B, C or HIV

Infection not adequately responding to appropriate therapy

History of malignancy other than localized tumors diagnosed more than one year previously and treated surgically with curative intent (for instance squamous cell or other skin cancers, stage 1 breast cancer, cervical carcinoma in situ, etc)

Moribund status or concurrent hepatic, renal, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy

History of congestive heart failure, arrhythmia, arterial or venous thrombosis (excluding line thrombosis) within the last 1 year, or myocardial infarction within 3 months before enrollment

Life expectancy of less than 3 months

ECOG Performance Status of 3 or greater

Hypersensitivity to eltrombopag or its components

Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential

Unable to understand the investigational nature of the study or give informed consent

Special Instructions:

Currently Not Provided

Keywords:

Promacta

Thrombocytopenia

Recruitment Keyword(s):

Myelodysplastic Syndrome

MDS

Thrombocytopenia

Condition(s):

Myelodysplastic Syndromes

Thrombocytopenia

Investigational Drug(s):

Eltrombopag

Investigational Device(s):

None

Intervention(s):

Drug: Eltrombopag

Supporting Site:

National Heart, Lung, and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Kantarjian H, Giles F, List A, Lyons R, Sekeres MA, Pierce S, Deuson R, Leveque J. The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer. 2007 May 1;109(9):1705-14

Houwerzijl EJ, Blom NR, van der Want JJ, Vellenga E, de Wolf JT. Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death. Leukemia. 2006 Nov;20(11):1937-42. Epub 2006 Sep 7

Kalina U, Hofmann WK, Koschmieder S, Wagner S, Kauschat D, Hoelzer D, Ottmann OG. Alteration of c-mpl-mediated signal transduction in CD34(+) cells from patients with myelodysplastic syndromes. Exp Hematol. 2000 Oct;28(10):1158-63

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