Treatment of Low Platelet Counts Due to advanced Myelodysplastic Syndrome or Acute Myeloid Leukemia with Eltrombopag

• Conditions: Thrombocytopenic Subjects with advanced Myelodysplastic Syndromes or Acute Myeloid Leukemia; MedDRA version: 17.0Level: LLTClassification code 10060356Term: Acute myeloid leukaemia without mention of remissionSystem Organ Class: 100000004864; MedDRA version: 17.0Level: LLTClassification code 10028534Term: Myelodysplastic syndrome NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000114-19-BE
• Lead Sponsor: GlaxoSmithKline Research and Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-09
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
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 Grade 4 thrombocytopenia, but 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 be stable and, in the opinion of the investigator, 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 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
11. 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 or urine 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subjects with MDS and an IPSS of low or intermediate-1 risk at screening.
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).
5. Leukocytosis =25,000/uL on Day 1 of treatment with study medication.
6. 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.
7. Female subjects who are nursing or pregnant (positive serum or urine ß-human chorionic gonadotropin [ß-hCG] pregnancy test) at screening or pre-dose on Day 1.
8. Current alcohol or drug abuse.
9. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
10. Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
11. Subjects infected Human Immunodeficiency Virus (HIV).
12. Subjects with liver cirrhosis (as determined by the investigator).
13. Subjects receiving or planned to receive any prohibited medication (see Section 6.2).
14. 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 subjects’ participation.
15. In France, subjects who have participated in any study using an investigational drug during the previous 30 days.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified