A Pilot Study of a Thrombopoietin-Receptor Agonist, Eltrombopag, in Patients With Low to Int-2 Risk Myelodysplastic Syndrome (MDS)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Myelodysplastic Syndromes Thrombocytopenia |
Drug: Eltrombopag |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Patients With Low to Int-2 Risk Myelodysplastic Syndrome (MDS) |
- 20,000/micro L increase in platelets above baseline and the toxicity profile at 3 months. [ Time Frame: 3 months after first dose medication ] [ Designated as safety issue: No ]
- Changes in platelet count (continuous variable), changes in platelet transfusion requirements, incidence of bleeding; changes in serum thrombopoietin level (as measured by enzyme-linked immunosorbent assay, R& D System)
| Estimated Enrollment: | 30 |
| Study Start Date: | July 2009 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
-
Drug: Eltrombopag
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
Diagnosis of MDS, with WHO classification of refractory cytopenia with unilineage dysplasia (RCUD), RARS, RCMD-RS, 5q- syndrome, or RCMD with refractory thrombocytopenia.
IPSS risk scores of low, intermediate-1, or intermediate-2.
Platelet count less than or equal to 30,000/ microL
Age greater than or equal to 18 years old
Disease that is refractory to, or relapsed after standard therapy for MDS as outlined in section 2.3, to include lenalidomide for deletion 5q- patients, and hypomethylating agents for non-deletion 5q- patients
Off all other treatments for MDS (except stable dosing of filgrastim [G-CSF], erythropoietin, and transfusion support) for at least four weeks. G-CSF can be used before, during and after the protocol treatment for subjects with documented neutropenia (< 500/UI) as long as they meet the criteria for thrombocytopenia as stated above. G-CSF must be held for 3 weeks prior to enrollment bone marrow biopsy and prior to each study assessment bone marrow biopsy.
Adequate liver function, as evidenced by total serum bilirubin less than or equal to 1.5 times the upper limit of normal patients with Gilbert's disease are eligible, provided intermittent indirect hyperbilirubinemia, AST or ALT less than or equal to 5 times the upper limit of normal.
A serum creatinine concentration less than or equal to 2 times ULN
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 percent
Bone marrow reticulin fibrosis of grade 3 or higher
Prior treatment with romiplostim or other TPO-R agonists, within (< ) 3 months of study entry
Treatment with horse or rabbit ATG or Campath within 6 months of study entry
Subjects with liver cirrhosis including subjects infected with Hepatitis B or C
Subjects with 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
Contacts and Locations| Contact: Barbara Weinstein, R.N. | (301) 594-4180 | weinsbar@nhlbi.nih.gov |
| Contact: Ronan G Desmond, M.D. | (301) 451-7143 | desmondrg@mail.nih.gov |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: Barbara Weinstein 301-594-4180 weinsbar@nhlbi.nih.gov | |
| Principal Investigator: | Ronan G Desmond, M.D. | National Heart, Lung, and Blood Institute (NHLBI) |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ) |
| ClinicalTrials.gov Identifier: | NCT00961064 History of Changes |
| Other Study ID Numbers: | 090199, 09-H-0199 |
| Study First Received: | August 15, 2009 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
Promacta Thrombocytopenia Myelodysplastic Syndrome MDS |
Additional relevant MeSH terms:
|
Myelodysplastic Syndromes Preleukemia Thrombocytopenia Bone Marrow Diseases |
Hematologic Diseases Precancerous Conditions Neoplasms Blood Platelet Disorders |
ClinicalTrials.gov processed this record on May 22, 2013