A randomized placebo-controlled phase 2 study of decitabine with or without eltrombopag in patients with acute myeloid leukemia =65 years of age not eligible for intensive chemotherapy

INTERVENTION:

Trade Name: Revolade Product Name: Eltrombopag Product Code: SB‐497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ELTROMBOPAG CAS Number: 496775‐61‐2 Current Sponsor code: SB‐497115 (Eltrombopag) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Eltrombopag Product Code: SB‐497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ELTROMBOPAG CAS Number: 496775‐61‐2 Current Sponsor code: SB‐497115 (Eltrombopag) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use

CONDITION:

acute myeloid leukemia AML ; MedDRA version: 20.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04]

PRIMARY OUTCOME:

Main Objective: To study whether supportive treatment with eltrombopag improves treatment change‐free survival (TCFS) in AML patients =65 years of age when added to standard treatment with DAC Primary end point(s): Treatment change‐free survival (TCFS) Secondary Objective: • overall survival (OS) ; • relapse free survival (RFS); • overall response rate (CR, PR, SD); • number of bone marrow blasts after 5, 9 and 12 months; • quality of life (QLQ‐C30 and SF‐36) ; • bleeding events; • median platelet counts; • number of platelet transfusions ; • hospitalization rate ; • safety and tolerability of treatment with EPAG / placebo; • impact of comorbidities on predicting overall survival Timepoint(s) of evaluation of this end point: date of treatment change or death

SECONDARY OUTCOME:

Secondary end point(s): • Overall Survival (OS) in presence of competing risk treatment change ; • Overall response rate (CR, PR, SD) ; • Relapse free survival (RFS) ; • Median platelet counts ; • Number of platelet transfusions during cycles 1‐4 ; • Incidence of bleeding events ; • Number of bone marrow blasts from baseline and after 5, 9 and 12 months ; • Hospitalization rate (days in hospital) ; • Safety and tolerability of treatment with EPAG / placebo ; • Quality of life ; • impact of comorbidities on predicting overall survival Timepoint(s) of evaluation of this end point: • whole study ; • date of relapse, death ; • cycles 1‐4, 5, 9 and 12 ; • follow up after treatment discontinuation: week 2, month 3, 6, 9, 12, 24, 36, and 48

INCLUSION CRITERIA:

• Newly diagnosed AML (including therapy‐related or after antecedent MDS) other than APL according to WHO criteria, i.e. bone marrow aspirate or biopsy must contain =20% blasts of all nucleated cells or differential blood count must contain =20% blasts. In AML defined by cytogenetic aberrations according to WHO the proportion of blasts may be <20% • Age = 65 years • ECOG performance status 0‐3 • Patients not eligible for intensive induction therapy • Planned therapy with DAC • Platelet count <75 Gpt/L taken within 4 weeks prior to randomization • Signed Informed Consent • Adequate liver function as assessed by the following laboratory requirements: o Total bilirubin = 3 times the upper limit of normal (except for Gilbert’s Syndrome) o ALT and AST = 3 times upper limit of normal Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) no F.1.2.1 Number of s