Study With Temsirolimus Added to Standard Chemotherapy for Patients Over 60 Years With Acute Myeloblastic Leukemia (TOR-AML)

Goethe University

Status and phase

Completed

Phase 2

Conditions

Acute Myeloblastic Leukemia

Treatments

Drug: sodium chloride solution 0.9%

Drug: temsirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT01611116

3066K1-1165

Details and patient eligibility

About

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.

Enrollment

33 patients

Sex

All

Ages

61+ years old

Volunteers

No Healthy Volunteers

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