To evaluate the long-term durability of clinicalbenefit as well as overall survival, the long-term safety and tolerability of eltrombopag in subjects with myelodysplastic syndromesand acute myeloid leukemia.
- Conditions
- Health Condition 1: null- Acute Myeloid Leukemia
- Registration Number
- CTRI/2012/08/002911
- Lead Sponsor
- GlaxoSmithKline Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other (Terminated)
- Sex
- Not specified
- Target Recruitment
- 140
1. 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.
2. Subjects must have Grade 4 thrombocytopenia (platelet counts <25 Gi/L) due to
bone marrow insufficiency (or platelet count >=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.
3. Subjects must have platelet count, bleeding and platelet transfusion data available
over a period of at least 4 weeks prior to randomization.
4. Prior systemic treatment for malignancy, with the exception of hydroxyurea (see
Section 6.1.2), 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.5. Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
6. Subjects must have stable disease (as defined by treatment guidelines and
investigator discretion) and, in the opinion of the investigator, must be expected to
complete a 12 week treatment period.
7. ECOG Status 0-2.
8. Subject must be able to understand and comply with protocol requirements and
instructions.
9. Subject has signed and dated an informed consent form.
10. Adequate baseline organ function defined by the criteria below:
• total bilirubin <= 1.5xULN except for Gilbertâ??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 <= 2.5xULN11. Women must be either of non-child bearing potential (see Section 7.3.12.2.1, for
definition) or women with child-bearing potential and men with reproductive
potential must be willing to practice acceptable methods of birth control during the
study (See Section 7.3.12.2, for acceptable methods of birth control). Women of
childbearing potential must have a negative serum pregnancy test within 7 days prior
to the first dose of study treatment.
12. 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.
1. Subjects with MDS and an IPSS of low or intermediate-1 risk.
2. Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or
AML secondary to a myeloproliferative neoplasm.
3. History of treatment with romiplostim or other TPO-R agonists.
4. Subjects with a QTc 480 msec (QTc 510 msec for subjects with Bundle Branch
Block) at baseline.
5. Subjects with a palpable spleen must have a splenic ultrasound to confirm spleen
length is <=16 cm. Subjects with palpable spleen 16 cm are not eligible.
6. Leukocytosis >=25,000/uL on Day 1 of treatment with study medication.
7. 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.
8. 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.
9. Current alcohol or drug abuse.
10. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.
11. Active and uncontrolled infections (e.g. sepsis).
12. Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
13. Subjects with liver cirrhosis (as determined by the investigator).
14. Subjects receiving or planned to receive any prohibited medication (see Section 6.2).15. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
drugs chemically related to eltrombopag or excipient (microcrystalline cellulose,
mannitol, polyvinylpyrrolidine, sodium starch glycolate, magnesium stearate,hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that
contraindicates the subjectsâ?? participation.
16. In France, subjects who have participated in any study using an investigational drug
during the previous 30 days.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective of this study is to determine the reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia and are treated with eltrombopag compared to those treated with placebo.Timepoint: The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment.
- Secondary Outcome Measures
Name Time Method