Leukemia, Myeloid, AcutePhase 1/2IDAMLNCT01518556
Safety and Efficacy Study of Idarubicin Dose Intensification to Treat Acute Myeloid Leukemia
A Phase 1/2 study testing Idarubicin in people with Leukemia, Myeloid, Acute, run by Konkuk University Medical Center at 1 site in South Korea.
Trial summary
The purpose of this study is to determine whether idarubicin dose intensification is safe and effective as a remission induction therapy for acute myeloid leukemia. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Idarubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2011to Mar 2025
- Phase
- Phase 1/2
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has been fully informed, has complete understanding fo this study, and has given voluntary written informed consent to comply with the protocol requirements.
- previously untreated de novo or secondary acute myeloid leukemia, including biphenotypic leukemia
- age between 20 and 65 years
- adequate organ functions, unless these abnormalities are attributable to leukemia
- left ventricular ejection fraction > 45%
- serum creatinine < 1.5 x upper limit of normal
Show all 9Show fewer
- total bilirubin < 1.5 x upper limit of normal
- alanine transferase and aspartate transferase < 2.5 x upper limit of normal if liver function abnormality is attributable to underlying leukemia, ALT and AST < 5 x upper limit of normal
- Eastern Cooperative Oncology Group performance status score of 0 to 2
Who cannot join
- hypersensitivity to the study drug
- any other malignancies within 3 years, except for cured non-melanoma skin cancer and curatively treated in situ carcinoma of the cervix
- New York Heart Association class III or IV heart failure, severe uncontrolled cardiac disease or myocardial infarction within the previous 6 months prior to the date of consent
- incapable of giving voluntary written informed consent to comply with the protocol requirements, which results from drug or alcohol intoxication, or neurological or psychiatric disorders
- pregnant or breastfeeding
- recent chemotherapy within 4 weeks prior to this study treatment
Show all 9Show fewer
- acute promyelocytic leukemia
- current or recent treatment with any other investigational medicinal product within 28 days prior to this study enrollment
- unsuitable for this study, in the investigator's opinion
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Division of Hematology-Oncology, Konkuk University Medical Center
Seoul, 143-729
About this study
Official title: Phase I/II Clinical Study of Idarubicin Dose Intensification for Remission Induction Therapy in Acute Myeloid Leukemia Patients Age of 65 Years or Less
The purpose of this study is to determine whether idarubicin dose intensification is safe and effective as a remission induction therapy for acute myeloid leukemia.
Read the detailed description
Up to nowadays, a standard induction therapy for acute myeloid leukemia(AML) has consisted of cytarabine 100-200 mg per square meter of body surface area(BSA) per day continuous infusion for 7 days with idarubicin 12 mg per square meter or daunorubicin 45 mg per square meter of BSA per day for 3 days. This standard therapy induces a complete remission(CR) in 50-75% of young adults and 40-50% of older adults. Recently two cooperative groups prospectively compared 45 mg per square meter of daunorubicin to 90 mg per square meter of BSA. They reported high-dose daunorubicin, as compared with a standard dose one, resulted in a significantly higher CR rate and improved overall survival(OS) up to age 65 without additional toxic effects.
Daunorubicin has been more commonly used anthracycline; however, idarubicin has a longer intracellular retention time and has shown more rapid clearance of marrow blasts. In the early 1990, three prospectively randomized studies showed that a combined regimen of idarubicin and cytarabine was superior to one of daunorubicin and cytarabine for the induction therapy of AML in adults. When they compared daunorubicin 45-50 mg per square meter with idarubicin 12-13 mg per square meter for induction therapy, there were no significant differences in hematologic and non-hematologic toxicities, including cardiac toxicity.
Phase I studies of idarubicin in patients with acute leukemia and chronic myelogenous leukemia in blast crisis reported the dose-limiting toxicities(DLT) were stomatitis and anorexia at the maximum tolerated dose(MTD) of 15 mg per square meter of BSA per day for 3 days. Based on the results of these studies, the investigators have generally administered idarubicin 12 mg per square meter per day for 3 days for the remission induction therapy of AML. Meanwhile Sanz et al. had administered idarubicin 12 mg per square meter per day for 4 days in patients with acute promyelocytic leukemia, and Tedeschi et al. had done a single high-dose idarubicin 40 mg per square meter combined with high-dose cytarabine 3 g per square meter per day for 5 days in patients with acute lymphoblastic leukemia, with no significant increase of severe toxicity. The MTD of idarubicin should be reevaluated in the treatment of acute leukemia, especially in the era of granulocyte colony-stimulating factor and better supportive care available.
In this phase I study, idarubicin 12 mg per square meter of BSA per day for 3 days will be given to three patients at the first stage and then the idarubicin dose will be increased by 3 mg per square meter of BSA each stage. The phase I study consists of 3 stages and the idarubicin dose will be increased up to 18 mg per square meter of BSA per day for 3 days unless DLTs do not develop in more than 33% of enrolled patients at each stage. In the subsequent phase II study, the MTD being determined from the phase I study or 18 mg per square meter of idarubicin will be given to the enrolled patients. There were three large studies which enrolled a total of 942 previously untreated adult patients with AML and in which idarubicin 12-13 mg per square meter of BSA per day for 3 days and cytarabine 100 mg per square meter daily for 7 days were administered intravenously. Therefore, the investigators can adopt them as historical control groups in terms of statistical assessment.
In conclusion, the investigators desire to determine the safety and effectiveness of the intensified dose of idarubicin in the treatment of acute myeloid leukemia through this phase I and II study.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Idarubicin
- Keywords
- Idarubicin, Remission Induction, Maximum Tolerated Dose, Survival
- 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.
IdarubicinDrug
Also called IDARU INJ
In the phase I study, idarubicin dose is increased step by step as follows: 12 mg/m2/day for 3 days IV in the 1st step; 15 mg/m2/day for 3 days IV in the 2nd step; 18 mg/m2/day for 3 days IV in the 3rd step.
In the phase II study, idarubicin dose is the maximum tolerated dose that is determined from the phase I study or 18 mg/m2/day for 3 days .
| Study group | Role | What they receive |
|---|---|---|
| Idarubicin | Experimental | Idarubicin dose intensification for remission induction in acute myeloid leukemia Receives: Drug: Idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of idarubicin in the phase I study.
The study design is adopted from traditional 3+3 design for phase I cancer clinical trials. The first three patients are treated at a starting dose (level 1). If none of the three patients experiences a DLT(dose-limiting toxicity), another group of three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a DLT, three more patients will be treated at the same dose level. The dose increment continues until at least two patients among a cohort of three to six patients experience DLTs.The maximum tolerated dose is defined as the dose level just below this toxic dose level.
Measured: Within 2 months after induction therapy in the phase I study.
Complete remission rate in the phase II study.
A complete remission designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1000 per microliter and platelets of more than 100000 per microliter. Hemoglobin concentration or hematocrit has no bearing on remission status, although the patient must be independent of transfusions.
Measured: Within 2 months after induction therapy therappy in the phase II study.
Secondary outcomes (2)
Dose-limiting toxicity in the phase I study.
Hematologic dose limiting toxicities (DLTs) are defined as the time to recovery of neutrophils (absolute neutrophil count of more than 500 per microliter) or platelets (platelet count of more than 20000 per microliter) exceeding 42 days after the start of induction therapy. Non-hematologic DLTs are defined as grade 4 or 5 toxicities.
Measured: Within 2 months after induction therapy in the phase I study.
Event-free survival and overall survival in the phase II study.
Event-free survival is defined for all patients and measured from the date of entry on study. It is measured until treatment failure, relapse from CR, or death from any cause, whichever occurs first. Overall survival is defined for all patients in a trial, and measured from the date of entry onto a study until death from any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored on the date he or she was last known to be alive.
Measured: Within 5 years after induction therapy in the phase II study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study startJul 2011
- Primary completionMar 2025
- Study completionMar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Konkuk University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Chung-Ang University Hospital, Seoul National University Hospital, Ewha Womans University, Samsung Medical Center, Chonbuk National University Hospital, Pusan National University Hospital, Hanyang University Seoul Hospital, Soon Chun Hyang University
- Responsible party
- Principal investigator, Mark Lee, Konkuk University Medical Center
- Investigators
- Mark H Lee, M.D., Ph.D., Principal investigator, Konkuk University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518556
- Sponsor's protocol ID
- AML-2011-01
- Acronym
- IDAML
- Status last verified
- Mar 2025
- First submitted
- 21 Jan 2012
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Study of Idarubicin Dose Intensification for Remission Induction Therapy in Acute Myeloid Leukemia Patients Age of 65 Years or Less
- ClinicalTrials.gov ID
- NCT01518556
- Acronym / sponsor ID
- IDAML / AML-2011-01
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- Idarubicin, Remission Induction, Maximum Tolerated Dose, Survival
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Konkuk University Medical CenterUniversity, hospital or other
- Collaborators
- Chung-Ang University Hospital, Seoul National University Hospital, Ewha Womans University, Samsung Medical Center, Chonbuk National University Hospital, Pusan National University Hospital, Hanyang University Seoul Hospital, Soon Chun Hyang University
- Study start
- Jul 2011 (actual)
- Primary completion
- Mar 2025 (actual)
- Study completion
- Mar 2025 (actual)
- First posted
- 26 Jan 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.
The purpose of this study is to determine whether idarubicin dose intensification is safe and effective as a remission induction therapy for acute myeloid leukemia.
Detailed description
Up to nowadays, a standard induction therapy for acute myeloid leukemia(AML) has consisted of cytarabine 100-200 mg per square meter of body surface area(BSA) per day continuous infusion for 7 days with idarubicin 12 mg per square meter or daunorubicin 45 mg per square meter of BSA per day for 3 days. This standard therapy induces a complete remission(CR) in 50-75% of young adults and 40-50% of older adults. Recently two cooperative groups prospectively compared 45 mg per square meter of daunorubicin to 90 mg per square meter of BSA. They reported high-dose daunorubicin, as compared with a standard dose one, resulted in a significantly higher CR rate and improved overall survival(OS) up to age 65 without additional toxic effects.
Daunorubicin has been more commonly used anthracycline; however, idarubicin has a longer intracellular retention time and has shown more rapid clearance of marrow blasts. In the early 1990, three prospectively randomized studies showed that a combined regimen of idarubicin and cytarabine was superior to one of daunorubicin and cytarabine for the induction therapy of AML in adults. When they compared daunorubicin 45-50 mg per square meter with idarubicin 12-13 mg per square meter for induction therapy, there were no significant differences in hematologic and non-hematologic toxicities, including cardiac toxicity.
Phase I studies of idarubicin in patients with acute leukemia and chronic myelogenous leukemia in blast crisis reported the dose-limiting toxicities(DLT) were stomatitis and anorexia at the maximum tolerated dose(MTD) of 15 mg per square meter of BSA per day for 3 days. Based on the results of these studies, the investigators have generally administered idarubicin 12 mg per square meter per day for 3 days for the remission induction therapy of AML. Meanwhile Sanz et al. had administered idarubicin 12 mg per square meter per day for 4 days in patients with acute promyelocytic leukemia, and Tedeschi et al. had done a single high-dose idarubicin 40 mg per square meter combined with high-dose cytarabine 3 g per square meter per day for 5 days in patients with acute lymphoblastic leukemia, with no significant increase of severe toxicity. The MTD of idarubicin should be reevaluated in the treatment of acute leukemia, especially in the era of granulocyte colony-stimulating factor and better supportive care available.
In this phase I study, idarubicin 12 mg per square meter of BSA per day for 3 days will be given to three patients at the first stage and then the idarubicin dose will be increased by 3 mg per square meter of BSA each stage. The phase I study consists of 3 stages and the idarubicin dose will be increased up to 18 mg per square meter of BSA per day for 3 days unless DLTs do not develop in more than 33% of enrolled patients at each stage. In the subsequent phase II study, the MTD being determined from the phase I study or 18 mg per square meter of idarubicin will be given to the enrolled patients. There were three large studies which enrolled a total of 942 previously untreated adult patients with AML and in which idarubicin 12-13 mg per square meter of BSA per day for 3 days and cytarabine 100 mg per square meter daily for 7 days were administered intravenously. Therefore, the investigators can adopt them as historical control groups in terms of statistical assessment.
In conclusion, the investigators desire to determine the safety and effectiveness of the intensified dose of idarubicin in the treatment of acute myeloid leukemia through this phase I and II study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Idarubicin | Experimental | Drug: IdarubicinIdarubicin dose intensification for remission induction in acute myeloid leukemia |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient has been fully informed, has complete understanding fo this study, and has given voluntary written informed consent to comply with the protocol requirements.
- previously untreated de novo or secondary acute myeloid leukemia, including biphenotypic leukemia
- age between 20 and 65 years
- adequate organ functions, unless these abnormalities are attributable to leukemia
- left ventricular ejection fraction > 45%
Key exclusion criteria (9 listed)
- hypersensitivity to the study drug
- any other malignancies within 3 years, except for cured non-melanoma skin cancer and curatively treated in situ carcinoma of the cervix
- New York Heart Association class III or IV heart failure, severe uncontrolled cardiac disease or myocardial infarction within the previous 6 months prior to the date of consent
- incapable of giving voluntary written informed consent to comply with the protocol requirements, which results from drug or alcohol intoxication, or neurological or psychiatric disorders
- pregnant or breastfeeding
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 |
|---|---|---|
| IdarubicinAlso: IDARU INJIn the phase I study, idarubicin dose is increased step by step as follows: 12 mg/m2/day for 3 days IV in the 1st step; 15 mg/m2/day for 3 days IV in the 2nd step; 18 mg/m2/day for 3 days IV in the 3rd step. In the phase II study, idarubicin dose is the maximum tolerated dose that is determined from the phase I study or 18 mg/m2/day for 3 days . | Drug | Idarubicin |
Primary outcome
Maximum tolerated dose of idarubicin in the phase I study.
Time frame: Within 2 months after induction therapy in the phase I study.
The study design is adopted from traditional 3+3 design for phase I cancer clinical trials. The first three patients are treated at a starting dose (level 1). If none of the three patients experiences a DLT(dose-limiting toxicity), another group of three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a DLT, three more patients will be treated at the same dose level. The dose increment continues until at least two patients among a cohort of three to six patients experience DLTs.The maximum tolerated dose is defined as the dose level just below this toxic dose level.
Complete remission rate in the phase II study.
Time frame: Within 2 months after induction therapy therappy in the phase II study.
A complete remission designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1000 per microliter and platelets of more than 100000 per microliter. Hemoglobin concentration or hematocrit has no bearing on remission status, although the patient must be independent of transfusions.
2 secondary outcomes
Dose-limiting toxicity in the phase I study.
Time frame: Within 2 months after induction therapy in the phase I study.
Event-free survival and overall survival in the phase II study.
Time frame: Within 5 years after induction therapy in the phase II study.
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 20 Mar 2025.
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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.
Mark H Lee, M.D., Ph.D. principal investigator
Konkuk University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Idarubicin in people with Leukemia, Myeloid, Acute, run by Konkuk University Medical Center at 1 site in South Korea.
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 9 inclusion and 9 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 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Maximum tolerated dose of idarubicin in the phase I study. (time frame: Within 2 months after induction therapy in the phase I study.). 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?
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 20 Mar 2025.