A Randomized Trial of a Combination of Nintedanib/Placebo in Combination With Induction Chemotherapy for Patients With Refractory or First Relapse Acute Myeloid Leukemia

Exclusion Criteria

• •Patient with documented acute promyelocytic leukemia and/or PML-RAR transcript.
• •Patient relapsing more than 2 years after initial remission.
• •Use of any active treatment for relapse including but not restricted to chemotherapy, targeted agents, hypomethylating agents or investigational drugs. Use of hydroxyurea up to 6g per day for cytoreduction is allowed for a maximum of 30 days prior treatment.
• •Patients with clinical evidence of active CNS disease at enrollment
• •LVEF below 45% or lifetime exposure to anthracyclines over 350mg/m2 of daunorubicin equivalent
• •Liver function tests: ASAT ALAT above 2.5 ULN, total bilirubin above 2.5 ULN in the absence of Hemolysis or diagnosis of Gilbert's syndrome
• •Serum creatinine above 2.0mg/dl
• •Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections, hepatitis. Any severe chronic disease potentially interfering with the protocol including HIV infection, active hepatitis B or C. It includes major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
• •Documented platelet refractoriness
• •Patient has a history of GI surgery, procedures or conditions that might interfere with the absorption or swallowing of the study drugs .
• •Women who are or pregnant, or who are currently breastfeeding
• •Prior treatment with nintedanib or any other VEGFR inhibitor
• •Known hypersensitivity to nintedanib, any other trial drug, or their excipients
• •Persistence of any clinically relevant (CTCAE grade 2 or above) non-hematological toxicities from previous AML therapy
• •Active alcohol or drug abuse
• •Any other condition that, according to the investigator, may forbid the administration of the idarubicin+cytarabine regimen
• •Therapeutic anticoagulation with INR modifying drug of or use of antiplatelet therapy (with the exception of low dose aspirin\<325mg/d)
• •Any other malignancies requiring an active treatment within the past year other than basal cell skin cancer or carcinoma in situ of the cervix. Patients actively treated with hormonotherapy for prostate cancer or breast cancer are eligible.