A study of eltrombopag in combination with azacitidine for subjects with low platelet counts due to intermediate 1, intermediate 2 or high risk Myelodysplastic Syndromes (MDS)
- Conditions
- Thrombocytopenic patients with myelodysplastic syndromesMedDRA version: 17.1Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.1Level: LLTClassification code 10028534Term: Myelodysplastic syndrome NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2013-000918-37-CZ
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
Subjects eligible for enrolment in the study must meet all of the following criteria. The eligibility criteria are to be met during the screening period, defined as the period up to 28 days prior to randomization on Day 1. Informed consent may be obtained >28 days before Day 1, if required, to allow time for receipt of cytogenetic results.
1. Age = 18 years. (For subjects in Taiwan, Age = 20 years).
2. MDS by World Health Organization (WHO) or French-American-British (FAB) classification.
3. Intermediate 1, intermediate 2 or high risk MDS by IPSS.
• A bone marrow for the determination of IPSS must be completed during the screening period, or within 3 months prior to randomization.
4. At least one platelet count < 75 Gi/L.
5. Eastern Cooperative Oncology Group (ECOG) Status 0-2.
6. Adequate baseline organ function defined by the criteria below
• total bilirubin less than 1.5x the upper limit of normal (ULN) except for Gilbert’s syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic] bilirubin in the absence of ALT abnormality)
• alanine aminotransferase (ALT) less than 2.5xULN
• creatinine less than 2.5xULN
7. Subjects with a QTc <450msec or <480msec for subjects with bundle branch block.
The QTc is the QT interval corrected for heart rate according to Fridericia’s formula (QTcF), machine or manual overread.
For subject eligibility and withdrawal, QTcF will be used.
For purposes of data analysis, QTcF will be used.
The QTc should be based on single or averaged QTc values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period
8. Subject is able to understand and comply with protocol requirements and instructions.
9. Subject has signed and dated informed consent.
10. 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.
11. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception
(as defined in Section 7.3.3) during the study and for 3 months following the last dose of study treatment.
12. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception (as described in Section 7.3.3) from time of randomization until 16 weeks after the last dose of study treatment.
13. French subjects: 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 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 192
Subjects meeting any of the following criteria at the time of randomization must not be enrolled in the study:
1. Previous treatment with hypomethylating agent or induction chemotherapy for MDS.
2. Proliferative type chronic myelomonocytic leukemia with white blood cell count
>12 Gi/L at any time during the 28 days before Day 1.
3. History of treatment with eltrombopag, romiplostim or other TPO-R agonists.
4. Previous allogeneic stem-cell transplantation.
5. 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.
6. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo).
7. Active and uncontrolled infections, including hepatitis B or C.
8. Human Immunodeficiency Virus (HIV) infection.
9. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects’ participation.
10. Pregnant or lactating female.
11. Any serious and/or unstable pre-existing medical (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures.
12. French subjects: the French subject has 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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method