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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Johann Wolfgang Goethe University Hospitals
Sponsor:
Information provided by (Responsible Party):
Christian Brandts MD, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01611116
First received: May 25, 2012
Last updated: May 29, 2013
Last verified: May 2013
  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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • median Event Free Survival (EFS) [ Time Frame: participants will be followed for one year after start of study treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 218
Study Start Date: May 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: December 2015 (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

Ages Eligible for Study:   61 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611116

Contacts
Contact: Christian Brandts, MD 0049-(0)69-6301 ext 7104 brandts@em.uni-frankfurt.de
Contact: Björn Steffen, MD 0049-(0)69-6301 ext 83965 steffen@em.uni-frankfurt.de

Locations
Germany
University Hospital Dresden Recruiting
Dresden, Germany, 01307
Johann Wolfgang Goethe University Hospital Recruiting
Frankfurt am Main, Germany, 60599
University Hospital Münster Recruiting
Münster, Germany, 48149
Sponsors and Collaborators
Christian Brandts MD
Investigators
Principal Investigator: Christian Brandts, MD Johann Wolfgang Goethe University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Christian Brandts MD, Study Director, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01611116     History of Changes
Other Study ID Numbers: 3066K1-1165
Study First Received: May 25, 2012
Last Updated: May 29, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on July 24, 2014