Study With Temsirolimus Added to Standard Chemotherapy for Patients Over 60 Years With Acute Myeloblastic Leukemia

NCT ID: NCT01611116

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2017-04-26

Brief Summary

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.

Conditions

Acute Myeloblastic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

sodium chloride solution 0.9%

Group Type: PLACEBO_COMPARATOR

sodium chloride solution 0.9%

Intervention Type: DRUG

intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment

temsirolimus

Group Type: EXPERIMENTAL

temsirolimus

Intervention Type: DRUG

intravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment

Interventions

sodium chloride solution 0.9%

intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment

Intervention Type: DRUG

temsirolimus

intravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment

Intervention Type: DRUG

Other Intervention Names

Torisel

Eligibility 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

• Minimum Eligible Age: 61 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Goethe University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Christian Brandts, MD

Study Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Brandts, MD

Role: STUDY_DIRECTOR

Goethe University

Locations

Charité University Hospital Berlin, Campus Benjamin Franklin

Berlin, , Germany

University Hospital Dresden

Dresden, , Germany

University Hospital Erlangen

Erlangen, , Germany

University Hospital Frankfurt

Frankfurt am Main, , Germany

University Hospital Münster

Münster, , Germany

Countries

Germany

References

Posting of Results in EUDRACT Database: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-002365-37/results

Reference Type: RESULT

Related Links

http://www.uct-frankfurt.de

University Cancer Center Frankfurt

http://www.kompetenznetz-leukaemie.de

German Competency Network for Leukemia

Other Identifiers

3066K1-1165

Identifier Type: -

Identifier Source: org_study_id