Safety Study of Eltrombopag Combined With Azacitidine to Treat Myelodysplastic Syndrome (MDS) (NMDSG10A)
Patients with Myelodysplastic Syndromes (MDS) often suffer from low platelet levels which may lead to bleeding complications. Treatment with cytotoxic agents can decrease the platelet levels further. Eltrombopag is a relatively new drug that increases the platelet level in the blood by working directly on the bone marrow. It is available for treatment of the disease Immunological Thrombocytopenic Purpura (ITP). In this study patients with MDS and low platelet levels that are treated with the cytotoxic agent Azacitidine will also receive Eltrombopag. The administration of Eltrombopag to MDS patients treated with Azacitidine may result in less dose reductions and less treatment delays for Azacitidine and may reduce the need for thrombocyte transfusions and lower the risk of bleeding complications.
This is a phase I study, meaning that our major goal is to investigate the safety and tolerability for Eltrombopag in this patient group. It will also generate a basis for a phase II-III-study.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Phase I Dose Finding Safety Study of a Thrombopoietin-receptor Agonist, Eltrombopag, in Patients With Myelodysplastic Syndrome Treated With Azacitidine|
- Safety and tolerability parameters [ Time Frame: week 26 ] [ Designated as safety issue: Yes ]
- Non-hematological clinical, laboratory Grade 3/Grade 4 toxicities
- Change in bone marrow or peripheral blood blast counts from baseline
- Adverse events and interactions at increasing doses of eltrombopag
- Azacitidine treatment delays and dose reductions [ Time Frame: week 26 ] [ Designated as safety issue: No ]
- Need for thrombocyte transfusions [ Time Frame: week 26 ] [ Designated as safety issue: No ]
- Bleeding complications [ Time Frame: week 26 ] [ Designated as safety issue: No ]
- Possible signs of antineoplastic effects (blood values and bone marrow picture) [ Time Frame: week 26 ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2011|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Experimental: Azacitidine + Eltrombopag||
In this study 4 different doses of oral eltrombopag (50mg, 100mg, 200mg and 300mg) will be tested. A modified 3+3 patient cohorts design will be used so no new patients are accepted to start on a higher dose without prior tolerance at the previous dose. Patients will be given eltrombopag once daily starting one week before the start of azacitidine treatment and then continue throughout the study, which duration will be approximately 3 months (three Azacytidine cycles). Patients will be evaluated continuously by clinical and laboratory assessments as well as bone marrow examinations during the treatment period until 4 weeks after discontinuation of Eltrombopag. Response, AEs/SAEs and DLTs will be monitored throughout the study.