Patients with newly diagnosed AML (except APL) according to the FAB and WHO classification, including AML evolving from MDS and AML after previous cytotoxic therapy or radiation (secondary AML) Bone marrow aspirate or biopsy must contain = 20% blasts of all nucleated cells, with the exception of AML FAB M6, where = 30% of non-erythroid cells must be leukemic blasts Age = 61 years MedDRA version: 17.0 Level: LLT Classification code 10000878 Term: Acute myeloblastic leukemia System Organ Class:
Conditions
Interventions
Trade Name: Torisel
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: TEMSIROLIMUS
CAS Number: 162635-04-3
Concentration unit: mg milligram(s)
Sponsors
J.W. Goethe-University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with 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 must contain = 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 =65 years) yes F.1.3.1 Number of subjects for this age range 112
Exclusion criteria
Exclusion criteria: • Patients who are not eligible for standard chemotherapy as described in chapter 6.2 • Previous treatment for AML, except leukapheresis for patients with hyperleukocytosis (leukocytes > 100,000/uL 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 extrasystoly 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 (creatinin 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to compare the median Event Free Survival (EFS)* and the EFS probability of all AML patients between the temsirolimus and the control group * EFS defined as: Time interval from day 1 of study treatment until treatment failure, relapse from CR or CRi, or death from any cause, whichever occurs first. The time point at which the patient is resistant to therapy or survives induction without a CR, CRi or morphologic leukemia-free state will be recorded.;Secondary Objective: compare • median Event Free Survival of patients with different cytogenetic and molecular risk groups (RG) • rate of early response after 1st induction of Temsirolimus group (TOR-G) vs control group (CG) • rate of early response after 1st induction of patients with different cytogenetic and mol. RG • CR rate of TOR-G vs CG • CR rate of patients with different cytogenetic and mol. RG • Relapse Free Survival (RFS) of TOR-G vs CG • RFS of patients with different cytogenetic and mol. RG • Overall Survival (OS) of TOR-G vs CG • OS of patients with different cytogenetic and mol. RG • rate of mol. remissions of TOR-G vs CG • toxicity of TOR-G and control treatment • rate of mol. relapse after mol. remission of TOR-G vs CG after induction therapy and during 1st remission • Evaluation of biomarkers indicating the course of disease, incl. genetic, epigenetic, transcriptional and protein markers, indicators of autophagy in leukemic blasts, bone marrow, periph. blood cells, serum and plasma ;Primary end point(s): Run-In-Part • optimal temsirolimus dose and schedule for the main part of the study Main Part • median Event Free Survival (EFS) and EFS probability;Timepoint(s) of evaluation of this end point: Run-In-Part at the end of the run-in-part Main Part at the end of the phase II main part (approx. three years after study start) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • rate of early response (= 10% bone marrow blasts on d15) after the first induction cycle of all AML patients • complete remission (CR) rate after induction therapy • median relapse-free survival (RFS) and RFS probability after reaching CR • median Overall Survival (OS) and OS probability • rate of molecular remissions and molecular relapses • toxicity according to CTC • biomarkers indicating the course of disease, including genetic, epigenetic, transcriptional and protein markers as well as indicators of autophagy in leukemic blasts, bone marrow, peripheral blood cells, serum and plasma;Timepoint(s) of evaluation of this end point: at the end of the phase II main part (approx. three years after study start) | — |
Countries
Germany
Contacts
Public ContactStudienzentrale Hämatologie
J.W. Goethe University Hospital
Outcome results
None listed