A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia (Part 1: Open-label, Part 2: Randomized, Double-blind, Part 3: Extension)
- Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%)
with thrombocytopenia due to bone marrow insufficiency from the disease or prior
treatment. Subjects with transient thrombocytopenia due to active treatment with
disease modifying agents or chemotherapy (except for hydroxyurea) are excluded
- Subjects must have Grade 4 thrombocytopenia (platelet counts <25 Gi/L) due to bone
marrow insufficiency (or Grade 4 thrombocytopenia, but platelet count greater than or
equal to 25 Gi/L due to platelet transfusion). In addition, subjects must have had
at least one of the following during the 4 week screening period: platelet
transfusion, or symptomatic bleeding or platelet count <10 Gi/L. Subjects whose
thrombocytopenia below 10 Gi/L is due to causes other than bone marrow insufficiency
(e.g., fever, infection, autoimmune disease) are not eligible.
- Subjects must have platelet count, bleeding and platelet transfusion data available
over a period of at least 4 weeks prior to randomization.
- Prior systemic treatment for malignancy, with the exception of hydroxyurea, must
have been discontinued prior to entry into the study: at least 4 weeks before Day 1
for the following: chemotherapy, demethylating agents (azacitidine or decitabine),
lenalidomide, thalidomide, clofarabine and IL-11(oprelvekin); at least 8 weeks before
Day 1 for antithymocyte/antilymphocyte globulin.
- Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
- Subjects must be stable and, in the opinion of the investigator, be expected to
complete a 12 week treatment period.
- ECOG Status 0-2.
- Subject must be able to understand and comply with protocol requirements and
- Subject has signed and dated an informed consent form.
- Adequate baseline organ function defined by the criteria below: total bilirubin ≤
1.5xULN except for Gilbert's syndrome or cases clearly not indicative of inadequate
liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of
ALT abnormality), ALT ≤ 3xULN, creatinine ≤ 2.5xULN
- Women must be either of non-child bearing potential or women with child-bearing
potential and men with reproductive potential must be willing to practice acceptable
methods of birth control during the study Women of childbearing potential must have a
negative serum or urine pregnancy test within 7 days prior to the first dose of study
- In France, a subject will be eligible for inclusion in this study only if either
affiliated to, or a beneficiary of, a social security category.
- Subjects with MDS and an IPSS of low or intermediate-1 risk at screening.
- Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML
secondary to a myeloproliferative neoplasm.
- History of treatment with romiplostim or other TPO-R agonists.
- Subjects with a QTc >480 msec (QTc >510 msec for subjects with Bundle Branch Block).
- Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication.
- Subjects with known thrombophilic risk factors. Exception: Subjects for whom the
potential benefits of participating in the study outweigh the potential risks of
thromboembolic events, as determined by the investigator.
- Female subjects who are nursing or pregnant (positive serum or urine β-human
chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1.
- Current alcohol or drug abuse.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.
- Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
- Subjects infected with Human Immunodeficiency Virus (HIV).
- Subjects with liver cirrhosis (as determined by the investigator).
- Subjects receiving or planned to receive any prohibited medication.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol,
polyvinylpyrrolidone, sodium starch glycolate, magnesium stearate, hypromellose,
titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates
the subjects' participation.
- In France, subjects who have participated in any study using an investigational drug
during the previous 30 days.