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A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
Not Recruiting
Trial ID: NCT01440374
Purpose
This was a worldwide, three-part (Part 1: open-label, Part 2: randomized, double-blind, Part
3: extension), multi-center study to evaluate the effect of eltrombopag in subjects with
myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who have thrombocytopenia due
to bone marrow insufficiency from their underlying disease or prior chemotherapy. This
objective was assessed by a composite primary endpoint that consists of the following: the
proportion of ≥Grade 3 hemorrhagic adverse events, or platelet counts <10 Gi/L, or platelet
transfusions. Patients with MDS or AML and Grade 4 thrombocytopenia due to bone marrow
insufficiency from their underlying disease or prior chemotherapy were enrolled in the study.
No low or intermediate-1 risk MDS subjects were enrolled in the study. Subjects must have had
at least one of the following during the 4 weeks prior to enrolment: platelet count <10 Gi/L,
platelet transfusion, or symptomatic hemorrhagic event. Supportive standard of care (SOC),
including hydroxyurea, was allowed as indicated by local practice throughout the study. The
study had 3 sequential parts. Subjects who were enrolled in Part 1 (open-label) cannot be
enrolled in Part 2 of the study (randomized, double-blind); however, subjects who completed
the treatment period for Part 1 or Part 2 (8 and 12 weeks, respectively) continued in Part 3
(extension) if the investigator determined that the subject was receiving clinical benefit on
treatment.
Official Title
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)
Stanford Investigator(s)
Peter Greenberg
Professor of Medicine (Hematology), Emeritus
Eligibility
Inclusion Criteria:
- 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
instructions.
- 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
treatment.
- In France, a subject eligible for inclusion in this study only if either affiliated
to, or a beneficiary of, a social security category.
Exclusion Criteria:
- 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.
Intervention(s):
drug: eltrombopag
drug: placebo
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
CCTO
650-498-7061