A Double-blind, Placebo-controlled, Randomized, Multicenter Phase II Trial to Assess the Efficacy of Temsirolimus Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML
Inclusion Criteria:
- Newly diagnosed AML (except APL) according to the FAB classification, including AML
evolving from MDS or other hematological diseases and AML after previous cytotoxic
therapy or radiation (secondary AML)
- Bone marrow aspirate or biopsy contains ≥ 20% blasts of all nucleated cells or
differential blood count must contain ≥ 20% blasts. In AML FAB M6 ≥ 30% of
non-erythroid cells in the bone marrow must be leukemic blasts. In AML defined by
cytogenetic aberrations the proportion of blasts may be < 20%.
- Age ≥ 61 years
- Informed consent, personally signed and dated to participate in the study
- Willingness of male patients whose sexual partners are women of child-bearing
potential (WOCBP), to use an effective form of contraception (pearl index < 1%)
during the study and at least 6 months thereafter.
Exclusion Criteria:
- Patients who are not eligible for standard chemotherapy
- Previous treatment for AML, except leukapheresis for patients with hyperleukocytosis
(leukocytes > 100,000/µl and / or leukostatic syndrome) or hydroxyurea
- Known central nervous system manifestation of AML
- Cardiac Disease: Heart failure NYHA III° or IV°; active coronary artery disease (MI
more than 6 months prior to study entry is permitted); serious cardiac ventricular
arrhythmias, defined as: ventricular extrasystoles grade LOWN IV, sustained or
non-sustained ventricular tachycardias, and history of ventricular fibrillation /
ventricular flutter, unless patient is protected by an internal cardioverter /
defibrillator or ventricular arrhythmia was attributable to a myocardial ischemia > 6
months before study entry.
- Chronically impaired renal function (creatinine clearance < 30 ml / min)
- Chronic pulmonary disease with relevant hypoxia
- Inadequate liver function (ALT and AST ≥ 2.5 x ULN) if not caused by leukemic
infiltration
- Total bilirubin ≥ 1.2 mg/dL if not caused by leukemic infiltration
- Uncontrolled active infection
- Concurrent malignancies other than AML with an estimated life expectancy of less than
two years and requiring therapy
- Known HIV and/or hepatitis C infection
- Evidence or history of CNS disease, including primary or metastatic brain tumors,
seizure disorders
- History of organ allograft
- Concomitant treatment with kinase inhibitors, angiogenesis inhibitors, calcineurin
inhibitors and Mylotarg
- Serious, non-healing wound, ulcer or bone fracture
- Allergy to study medication or excipients in study medication
- Investigational drug therapy outside of this trial during or within 4 weeks of study
entry
- Any severe concomitant condition which makes it undesirable for the patient to
participate in the study or which could jeopardise compliance with the protocol