Patients with poor graft function after allogeneic-hematopoietic stem cells transplantation (allo-HSCT). Patients diagnosed with primary or secondary poor graft function (PGF) defined as two or more cytopenias after day +30 post-transplant: Platelet count <20,000/ µL (mandatory), absolute neutrophil count (ANC) <1,000/µL, Hemoglobin <100 g/L. MedDRA version: 20.0 Level: LLT Classification code 10067862 Term: Allogeneic stem cell transplantation System Organ Class: 100000004865
Conditions
Sponsors
Novartis Farmacéutica S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must provide written, signed and dated informed consent form before any study assessment is performed 2. Male of female patients = 18 years of age 3. Patients diagnosed with primary or secondary poor graft function (PGF) defined as two or more cytopenias after day +30 post-transplant (re-tested in a peripheral blood analysis at screening): a. Platelet count 90% of donor chimerism. 5. Karnofsky status =90% 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 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Pregnant or nursing (lactating women). 2. Evidence of active acute or chronic graft versus host disease (GVHD). 3. Evidence of any clonal abnormality on cytogenetics (in the screening bone marrow analysis). 4. Evidence of bone marrow involvement or progression of the underlying disease assessed by sensitive methods (flow cytometry and/or molecular methods). 5. Evidence of thrombotic microangiopathy. 6. Evidence of possible causes of cytopenias other than PGF (active infections, mielotoxic drugs, hypersplenism…). 7. Prior use of any thrombopoietin receptor (TPO-R) agonists for PGF. 8. AST or ALT levels >3 x ULN. 9. Creatinine level =1.5 x ULN. 10. Total bilirubin level =1.5 x ULN. 11. Previous thromboembolic event. 12. Hypersensitivity to eltrombopag or its components. 13. Severe heart disease, significant abnormally ECG in screening visit or congenital long QT syndrome. 14. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of eltrombopag for poor graft function on overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of eltrombopag.;Secondary Objective: 1. To determine the response in each haematological lineage separately 2. To evaluate the long-term efficacy of eltrombopag on overall hematologic response (partial and complete) at 24 and 36 weeks after the initiation of eltrombopag. 3. To evaluate the transfusion independence for red blood cells (RBC) and/or platelets after the initiation of eltrombopag (see Section Efficacy assessments for endpoint) 4. To evaluate the reduction and discontinuation of concomitant granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin (EPO) therapy (see Section Efficacy assessments for endpoint). 5. To evaluate the overall survival and survival rate at 24 and 36 weeks 6. To evaluate the safety of eltrombopag. Safety will be assessed by frequency and severity of adverse events (AEs), serious AEs (SAEs) based on the Common Terminology Criteria for AEs (CTCAE v4.03) and AEs leading to discontinuation.;Primary end point(s): The primary efficacy endpoint is the percentage of patients who have a response (partial and complete), by 16 weeks after the initiation of eltrombopag.;Timepoint(s) of evaluation of this end point: Week 16. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of patients who have a response in the neutrophil lineage (defined as ANC >1,000/ µL or = 1500/ µL, confirmed in two consecutive blood tests separated a minimum of 7 days. - Percentage of patients who have a response in the platelet lineage (defined as Platelet count >20,000/µL or = 100000/µL , confirmed in two consecutive blood tests separated a minimum of 7 days. - Percentage of patients who have a response in the hemoglobin lineage (defined as Hb >100 g/L or = 110 g/ L , confirmed in two consecutive blood tests separated a minimum of 7 days. - Percentage of patients who maintain a partial or complete response at 24 and 36 weeks - Percentage of patients previously transfusion-dependent who do no longer require platelets and/or RBC transfusions before and after the first 16 weeks of treatment with eltrombopag. - Time period in which patients do not receive platelets and/or RBC transfusions. - Percentage of patients who discontinue or reduce by =50% the use of concomitant G-CSF and/or EPO therapy. - Overall survival. - Overall survival rate at weeks 24 and 36.;Timepoint(s) of evaluation of this end point: week 24 and week 36 | — |
Countries
Spain
Contacts
Public ContactTrial Monitoring Organization (TMO)
Novartis Farmacéutica S.A.
Outcome results
None listed