Acute Myeloblastic LeukemiaPhase 2TOR-AMLNCT01611116
Study With Temsirolimus Added to Standard Chemotherapy for Patients Over 60 Years With Acute Myeloblastic Leukemia
A Phase 2 study testing sodium chloride solution 0.9% and temsirolimus in people with Acute Myeloblastic Leukemia, run by Goethe University at 5 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 61 years and older
- Conditions the study is for
- Acute Myeloblastic Leukemia
- What is being tested?
- sodium chloride solution 0.9% and temsirolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 5 sitesGermany
- Study dates
- May 2012to 26 Apr 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 61 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Charité University Hospital Berlin, Campus Benjamin Franklin
Berlin, 10117
University Hospital Dresden
Dresden, 01307
University Hospital Erlangen
Erlangen, 91054
University Hospital Frankfurt
Frankfurt am Main, 60590
University Hospital Münster
Münster, 48149
About this study
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
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
- Being tested
- sodium chloride solution 0.9%, temsirolimus
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium chloride solution 0.9%Drug
intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment
temsirolimusDrug
Also called Torisel
intravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment
| Study group | Role | What they receive |
|---|---|---|
| sodium chloride solution 0.9% | Placebo comparator | Not described Receives: Drug: sodium chloride solution 0.9% |
| temsirolimus | Experimental | Not described Receives: Drug: temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: participants will be followed for one year after start of study treatment
Complete Remission (CR) rate in the temsirolimus and the control group
Measured: participants will be followed for one year after start of study treatment
CR rate of AML patients with different cytogenetic and molecular risk groups
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: participants will be followed for one year after start of study treatment
rate of molecular remissions in the temsirolimus and the control group
Measured: participants will be followed for one year after start of study treatment
Number of adverse events in the temsirolimus and the control group
Measured: 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
Measured: participants will be followed for one year after start of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2012 (estimated)
- Study startMay 2012
- Primary completion26 Apr 2017
- Study completion26 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Goethe University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Christian Brandts, MD, Goethe University
- Investigators
- Christian Brandts, MD, Study director, Goethe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611116
- Sponsor's protocol ID
- 3066K1-1165
- Acronym
- TOR-AML
- Status last verified
- May 2023
- First submitted
- 25 May 2012
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Posting of Results in EUDRACT Database: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-002365-37/results
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01611116
- Acronym / sponsor ID
- TOR-AML / 3066K1-1165
- Conditions
- Acute Myeloblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Goethe UniversityUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- 26 Apr 2017 (actual)
- Study completion
- 26 Apr 2017 (actual)
- First posted
- 4 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sodium chloride solution 0.9% | Placebo comparator | Drug: sodium chloride solution 0.9% |
| temsirolimus | Experimental | Drug: temsirolimus |
Who may qualify
- Ages
- 61 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium chloride solution 0.9%intravenous application added to standard chemotherapy on up to 8 predefined days during the course of study treatment | Drug | sodium chloride solution 0.9% |
| temsirolimusAlso: Toriselintravenous application added to standard chemotherapy on up to 16 predefined days during the course of study treatment | Drug | temsirolimus |
Primary outcome
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.
12 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Results publicationPosting of Results in EUDRACT Database: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-002365-37/results
- University Cancer Center FrankfurtLink provided by the sponsor.
- German Competency Network for LeukemiaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Brandts, MD study director
Goethe University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sodium chloride solution 0.9% and temsirolimus in people with Acute Myeloblastic Leukemia, run by Goethe University at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
median Event Free Survival (EFS) (time frame: participants will be followed for one year after start of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01611116, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.