Study With Temsirolimus Added to Standard Chemotherapy for Patients Over 60 Years With Acute Myeloblastic Leukemia
Acute Myeloblastic Leukemia
Conditions: official terms
Leukemia, Myeloid - Leukemia, Myeloid, Acute
Study Type
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Name: sodium chloride solution 0.9% Type: Drug
Name: temsirolimus Type: Drug
Overall Status
Standard chemotherapy is capable of eliminating most leukemic blasts in acute myeloblastic leukemia (AML), while leukemia-initiating cells are not sufficiently eradicated. As a consequence, refractory disease and relapse frequently occur in AML, especially in elderly patients. The investigators propose that the addition of temsirolimus may improve standard AML chemotherapy. Furthermore, temsirolimus may specifically target the leukemia-initiating cells in AML, thereby reducing the risk of leukemia relapse.

The study's main part is preceded by a open label run-in part, in which optimal temsirolimus dose and schedule for the main part o the study will be determined.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 61 Years
Gender: Both
Criteria: 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
Charité University Hospital Berlin, Campus Benjamin Franklin
Berlin, Germany
Status: Recruiting
Contact: Claudia Baldus, Prof.
University Hospital Dresden
Dresden, Germany
Status: Recruiting
Contact: Christoph Röllig, MD
University Hospital Erlangen
Erlangen, Germany
Status: Recruiting
Contact: Stefan Krause, Prof.
University Hospital Frankfurt
Frankfurt am Main, Germany
Status: Recruiting
Contact: Christian Brandts, MD
University Hospital Münster
Münster, Germany
Status: Recruiting
Contact: Tim Sauer, MD
Start Date
May 2012
Completion Date
December 2017
Christian Brandts MD
Johann Wolfgang Goethe University Hospitals
Record processing date processed this data on July 28, 2015 page