First-line severe aplastic anaemia MedDRA version: 19.0 Level: PT Classification code 10002967 Term: Aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Novartis Farmacéutica, S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed. 2.Patient is male/female =6 years old at the time of informed consent and able to swallow a tablet. 3.Patient has SAA characterized by: a.Bone marrow cellularity =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1.Diagnosis of Fanconi anemia. 2.Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with very severe neutropenia (ANC 3 x ULN. 6.Creatinine, total bilirubin, and alkaline phosphatase >3 x ULN . 7.Patient with liver cirrhosis. 8.Infection not adequately controlled with appropriate therapy. 9.Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient’s ability to consent, be compliant with study procedures, tolerate protocol therapy, or that death within 30 days is likely. 10.Patients with cancer who are not considered cure, are on active chemotherapeutic treatment or who take drugs with hematological effects. 11.Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment. 12.Pregnancy statements and contraception requirements: Pregnancy or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant (or female partners of male patients), unless they are using highly effective methods of contraception during dosing and for 3 months after stopping medication. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. 13.Not able to understand the investigation nature of the study or to give informed consent. 14.Clinically significant ECG abnormality including cardiac arrhythmias (e. g. ventricular tachycardia) complete left bundle branch block, high grade atrioventricular block, or inability to determine the QTcF interval on the ECG. 15.Presence of cardiac disease, or family history of idiopathic sudden death or congenital long QT syndrome. 16.Risk factors for Torsades de Pointe including uncorrected hypokalemia or hypomagnesemia, or use of concomitant medication(s) with a known risk to prolong the QT interval that cannot be discontinued.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of eltrombopag + cyclosporine as first-line therapy on overall hematologic response (neutrophil, platelet, hemoglobin) by 6 months;Secondary Objective: Obj. 1: Evaluate the effect of ETB + CsA on overall hematologic response (neutrophil, platelet, hemoglobin) by 3 and 12 months All of the following secondary objectives will be assessed by 6 months, 30 months and 60 months as appropriate and will be reported in a cumulative basis Obj. 2: Evaluate the duration of hematologic response Obj. 3: Evaluate disease relapse rate Obj. 4: Evaluate the clonal evolution to myelodysplasia, paroxysmal nocturnal hemoglobinuria (PNH), and leukemia Obj. 5: Evaluate the need for blood transfusion Obj. 6: Evaluate the need for platelet transfusion Obj. 7: Evaluate the duration of platelet and blood transfusion independence Obj. 8: Evaluate overall survival (OS) Obj. 9: Evaluate the effect of ETB and CsA on patient symptoms and health related quality of life Obj. 10: Evaluate the safety and tolerability of ETB + CsA Obj. 11: Characterize the PK of ETB when combined to CsA;Primary end point(s): Primary analysis will be done after all the patients enrolled have completed 6 months of treatment with eltrombopag+cyclosporine or discontinued treatment with eltrombopag prior to 6 months for evaluating the primary endpoint.;Timepoint(s) of evaluation of this end point: The primary objective of the study is to evaluate the eltrombopag + cyclosporine as first-line therapy as assessed by the overall hematologic response rate by 6 months. Bayesian approach will be used for analysis of the primary endpoint. The primary analysis will be based on the calculation of observed overall hematologic response rate by 6 months and its posterior distribution using a beta-binomial model. Combination therapy of eltrombopag + cyclosporine will be declared efficacious if the following criteria are met: a. Observed hematologic ORR = “clinically meaningful” threshold (30%) b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Second analysis will be done after all the patients enrolled have completed 30 months of treatment with cyclosporine or discontinued treatment with cyclosporine prior to 30 months.;Timepoint(s) of evaluation of this end point: The primary analysis will be conducted and the primary CSR will be written 6 M (months) after all the patients enrolled have completed 6 M of treatment with eltrombopag+cyclosporine or discontinued treatment with eltrombopag prior to 6 M. The second CSR will be written based on the cumulative data obtained after all the patients enrolled have completed 30 M tapering of cyclosporine or discontinued treatment with cyclosporine prior to 30 M. The final analysis will be done after all the patients enrolled completed 60 M in the study or discontinued the study prior to 60 M, based on which the final CSR will be written. Overall survival will be reported by 6 months (EOT with Eltrombopag), by 30 M (EOT with Cyclosporine) and by the completion of 60 M (end of study). | — |
Countries
Brazil, Canada, France, Hong Kong, Hungary, India, Italy, Korea, Republic of, Mexico, Netherlands, Qatar, Spain, Turkey
Contacts
Public ContactDepartamento Médico (GMO)
Novartis Farmacéutica, S.A
Outcome results
None listed