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

Acute Myeloblastic Leukemia Clinical Trial

— TOR-AML  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01611116
• Other study ID #: 3066K1-1165
• Status: Completed
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: April 26, 2017

Study information

• Verified date: May 2023
• Source: Goethe University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: April 26, 2017
• Est. primary completion date: April 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloblastic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• sodium chloride solution 0.9%
intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment
• temsirolimus
intravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment

Locations

Country	Name	City	State
Germany	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

Sponsors (1)

Lead Sponsor	Collaborator
Goethe University

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	median Event Free Survival (EFS)	Event Free Survival defined as time interval from day 1 of study treatment until treatment failure, relapse from complete remission (CR) or incomplete remission (CRi), or death from any cause, whichever occurs first.	participants will be followed for one year after start of study treatment
Primary	event free survival probability	Event Free Survival defined as time interval from day 1 of study treatment until treatment failure, relapse from complete remission (CR) or incomplete remission (CRi), or death from any cause, whichever occurs first.	participants will be followed for one year after start of study treatment
Secondary	median Event Free Survival (EFS) of AML patients with different cytogenetic and molecular risk groups		participants will be followed for one year after start of study treatment
Secondary	rate of early response after the first induction cycle in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	rate of early response of AML patients with different cytogenetic and molecular risk groups		participants will be followed for one year after start of study treatment
Secondary	Complete Remission (CR) rate in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	CR rate of AML patients with different cytogenetic and molecular risk groups		participants will be followed for one year after start of study treatment
Secondary	Relapse Free Survival (RFS) of AML patients in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	Relapse Free Survival (RFS) of AML patients with different cytogenetic and molecular risk groups		participants will be followed for one year after start of study treatment
Secondary	Overall Survival (OS) of all AML patients in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	Overall Survival (OS) of AML patients with different cytogenetic and molecular risk groups		participants will be followed for one year after start of study treatment
Secondary	rate of molecular remissions in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	Number of adverse events in the temsirolimus and the control group		participants will be followed for one year after start of study treatment
Secondary	rate of molecular relapse after molecular remission of all AML patients in the temsirolimus and the control group after induction therapy and in the course of the first remission		participants will be followed for one year after start of study treatment

External Links

•   German Competency Network for Leukemia
•   University Cancer Center Frankfurt