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

NCT01611116 | Completed Phase 2 DMC

• 1 other identifier: 3066K1-1165
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• 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

• 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

• 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

• Complete Remission (CR) rate in the temsirolimus and the control group

  participants will be followed for one year after start of study treatment

• CR rate of AML patients with different cytogenetic and molecular risk groups

  participants will be followed for one year after start of study treatment

Study Arms (2)

sodium chloride solution 0.9%

PLACEBO COMPARATOR

Drug: sodium chloride solution 0.9%

temsirolimus

EXPERIMENTAL

Drug: temsirolimus

Interventions

sodium chloride solution 0.9% DRUG

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

sodium chloride solution 0.9%

temsirolimus DRUG

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

Also known as: Torisel

temsirolimus

Eligibility Criteria

• Age: 61 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Goethe University: lead

Study Sites (5)

Charité University Hospital Berlin, Campus Benjamin Franklin

Berlin, 10117, Germany

Location

University Hospital Dresden

Dresden, 01307, Germany

Location

University Hospital Erlangen

Erlangen, 91054, Germany

Location

University Hospital Frankfurt

Frankfurt am Main, 60590, Germany

Location

University Hospital Münster

Münster, 48149, Germany

Location

Related Publications (1)

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

  RESULT

Related Links

• University Cancer Center Frankfurt
• German Competency Network for Leukemia

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Christian Brandts, MD

  Goethe University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Director

Study Record Dates

• First Submitted: May 25, 2012
• First Posted: June 4, 2012
• Study Start: May 1, 2012
• Primary Completion: April 26, 2017
• Study Completion: April 26, 2017
• Last Updated: May 24, 2023

Record last verified: 2023-05

Locations

DE (5)