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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01611116
First Posted: June 4, 2012
Last Update Posted: August 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Christian Brandts MD, Johann Wolfgang Goethe University Hospital
  Purpose

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.


Condition Intervention Phase
Acute Myeloblastic Leukemia Drug: sodium chloride solution 0.9% Drug: temsirolimus Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Christian Brandts MD, Johann Wolfgang Goethe University Hospital:

Primary Outcome Measures:
  • median Event Free Survival (EFS) [ Time Frame: participants will be followed for one year after start of study treatment ]
    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.

  • event free survival probability [ Time Frame: participants will be followed for one year after start of study treatment ]
    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.


Secondary Outcome Measures:
  • median Event Free Survival (EFS) of AML patients with different cytogenetic and molecular risk groups [ Time Frame: participants will be followed for one year after start of study treatment ]
  • rate of early response after the first induction cycle in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • rate of early response of AML patients with different cytogenetic and molecular risk groups [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Complete Remission (CR) rate in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • CR rate of AML patients with different cytogenetic and molecular risk groups [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Relapse Free Survival (RFS) of AML patients in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Relapse Free Survival (RFS) of AML patients with different cytogenetic and molecular risk groups [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Overall Survival (OS) of all AML patients in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Overall Survival (OS) of AML patients with different cytogenetic and molecular risk groups [ Time Frame: participants will be followed for one year after start of study treatment ]
  • rate of molecular remissions in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • Number of adverse events in the temsirolimus and the control group [ Time Frame: participants will be followed for one year after start of study treatment ]
  • 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 [ Time Frame: participants will be followed for one year after start of study treatment ]

Enrollment: 33
Study Start Date: May 2012
Study Completion Date: April 26, 2017
Primary Completion Date: April 26, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: sodium chloride solution 0.9% Drug: sodium chloride solution 0.9%
intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment
Experimental: temsirolimus Drug: temsirolimus
intravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment
Other Name: Torisel

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   61 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01611116


Locations
Germany
Charité University Hospital Berlin, Campus Benjamin Franklin
Berlin, Germany, 10117
University Hospital Dresden
Dresden, Germany, 01307
University Hospital Erlangen
Erlangen, Germany, 91054
University Hospital Frankfurt
Frankfurt am Main, Germany, 60590
University Hospital Münster
Münster, Germany, 48149
Sponsors and Collaborators
Christian Brandts MD
Investigators
Study Director: Christian Brandts, MD University Hospital, Frankfurt
  More Information

Additional Information:
Responsible Party: Christian Brandts MD, Study Director, Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier: NCT01611116     History of Changes
Other Study ID Numbers: 3066K1-1165
First Submitted: May 25, 2012
First Posted: June 4, 2012
Last Update Posted: August 21, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents