This study is NOT currently recruiting participants.
Number
09-H-0199
Sponsoring Institute
National Heart, Lung and Blood Institute (NHLBI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
Yes
Population Exclusion(s)
Children
Keywords
Hematopoiesis; Autoimmunity; megakaryocyte; Bone Marrow Fibrosis; Thrombocytopenia
Recruitment Keyword(s)
Myelodysplastic Syndrome; MDS; Thrombocytopenia
Condition(s)
Thrombocytopenia; Myelodysplastic Syndrome (MDS)
Investigational Drug(s)
eltrombopag (Promacta)
Investigational Device(s)
None
Intervention(s)
Drug: Eltrombopag
Supporting Site
National Heart, Lung, and Blood Institute
- 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.
-Platelet count 30,000/ L or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); OR hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC 500
Design:
- Treatment with eltrombopag tablets once per day for 16-20 weeks.
- 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.
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INCLUSION CRITERIA: Diagnosis of MDS, with WHO classification of refractory anemia, refractory cytopenia with unilineage dysplasia (RCUD), RARS, RCMD-RS, or RCMD. IPSS risk scores of low, intermediate-1, or intermediate-2. Platelet count less than or equal to 30,000/ microL or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); or hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC less than or equal to 500 Age greater than or equal to 18 years old Treatment naive or 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 other cytopenia 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, unless clinically indicated to avoid infections per PI discretion. 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 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 treated with chemotherapy and cytogenetic abnormalities suggestive of secondary myelodysplasia. 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 Life expectancy of less than 3 months 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 or does not have a legally authorized representative or surrogate that can provide informed consent per section
Diagnosis of MDS, with WHO classification of refractory anemia, refractory cytopenia with unilineage dysplasia (RCUD), RARS, RCMD-RS, or RCMD.
IPSS risk scores of low, intermediate-1, or intermediate-2.
Platelet count less than or equal to 30,000/ microL or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); or hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC less than or equal to 500
Age greater than or equal to 18 years old
Treatment naive or 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 other cytopenia 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, unless clinically indicated to avoid infections per PI discretion.
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
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 treated with chemotherapy and cytogenetic abnormalities suggestive of secondary myelodysplasia.
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
Life expectancy of less than 3 months
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 or does not have a legally authorized representative or surrogate that can provide informed consent per section
Principal Investigator
Referral Contact
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