Phase 2 study design and patients
inadequate liver, death, chronic or active hepatitis C, AML, bone marrow blast count, infections, fractures, trauma
UNCONTROLLED HYPERTENSION, INFILTRATION, INFECTIONS, AML, ACUTE PROMYELOCYTIC LEUKEMIA, REMISSION, DISEASES
The trial was registered at The primary objective was to evaluate whether nintedanib, when combined with LDAC, improved overall survival (OS) of patients with previously untreated or r/r AML compared to LDAC plus placebo. OS was defined as the time interval from day one of study treatment to the day of death. For a patient who was not known to have died by the end of follow-up, observation of OS was censored on the date the patient was last known to be alive. Secondary and exploratory objectives were complete remission (CR) rate, overall response rate consisting of CR, CR with incomplete hematological recovery (CRi) and CR with incomplete platelet recovery (CRp) by International Working Group (IWG) criteria [Patients 60 years or older with newly diagnosed or r/r AML who were ineligible for intensive chemotherapy were enrolled. Ineligibility for intensive therapy was based on investigator assessment of AML characteristics (e.g., genetics, type of AML) and patient characteristics (e.g., age, comorbidities, performance status). Exclusion criteria were acute promyelocytic leukemia, bone marrow blast count of less than 30% (at the time of study onset qualifying for azacitidine therapy), inadequate liver (ALT, AST ≥ 1.5 × ULN if not due to AML infiltration) and renal (creatinine clearance < 45 mL/min) function, central nervous system (CNS) involvement of AML, chronic or active hepatitis C, uncontrolled hypertension (> 160 mmHg systolic, > 95 mmHg diastolic), larger trauma or surgery within the last 4 weeks, chronic wound healing problems including bone fractures, uncontrolled infections, previous therapy with tyrosine kinase inhibitors or angiogenesis inhibitors, specific contraindications against cytarabine or nintedanib, relevant other diseases possibly influencing study endpoints, and participation in another interventional clinical trial within 4 weeks. All patients provided written informed consent prior to trial enrollment.Patients were randomized in a 1:1 ratio to receive either LDAC plus nintedanib or LDAC plus placebo, stratified by AML status (newly diagnosed versus r/r).