Acute Myelogenous LeukemiaPhase 1NCT00382954
Phase I Using Velcade & Idarubicin in Elderly and Relapsed AML
A Phase 1 study testing Velcade and Idarubicin in people with Acute Myelogenous Leukemia, run by University of Kentucky at 2 sites in United States.
Trial summary
The purpose of this study is to determine the maximal tolerated dose (MTD) of bortezomib and idarubicin given in combination to newly diagnosed AML patients >60 years or relapsed AML patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Velcade and Idarubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2004to Oct 2008
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: > 60 years of age for newly diagnosed/transformed disease; > 18 years of age for relapsed disease.
- AML with or without antecedent hematologic disorder diagnosed by morphologic, histochemical, or cell surface marker criteria - as defined by the WHO classification (17).
- Newly diagnosed, elderly patients who are considered unsuitable for intensive chemotherapy induction -- antecedent hematologic disorders, pre-existing myelodysplasia, trilineage dyspoiesis, unfavorable cytogenetics, or pre-existing comorbidities.
- Untreated conditions meeting criteria the first and third criteria or patients with diagnosis as in criteria 2 who have relapsed after at least one successful induction therapy. (Relapsed patients treated on this protocol will be patients without a suitable donor for transplant or for whom transplant is not an option for other reasons.)
- Karnofsky performance status >60.
- Adequate cardiac function as evidenced by an ejection fraction on MUGA >/= 40, as well as no evidence of uncontrolled hypertension, New York Heart Class III/IV congestive heart failure, angina pectoris, or ventricular dysrhythmias.
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- Adequate renal function as evidenced by a calculated creatinine clearance >/= 30ml/min (Cockcroft-Gault formula).
- Adequate pulmonary function as evidenced by room air and exercise saturations >/= 92 or DLCO >/= 40% or FEV1 >/= 60% of predicted.
- Adequate liver function as evidenced by SGOT/SGPT less than 5 times the ULN and total Bilirubin less than 2 times the ULN except where abnormalities are directly attributable to leukemia.
- Adequate neurologic function -- patients must be currently free of active CNS leukemia as evidenced by cytospin of CSF from lumbar puncture if there is any clinical suspicion for CNS leukemia. As well, patients must not have >/= grade 2 neuropathy by NCI common toxicity criteria (CTC), Version 3.0.
- Prior anthracycline dose in relapsed patients must not exceed 72 mg/m^2 of idarubicin or any dose equivalent to 300 mg/m^2 of adriamycin.
- Patients must be informed and sign a written consent.
Who cannot join
- Patients with acute promyelocytic leukemia. Patients with uncontrolled systemic infection.
- Patients who are known to be HIV seropositive.
- Patients with evidence of CNS leukemia.
- Patients who are pregnant or lactating.
- Patients with primarily refractory disease unresponsive to a standard induction regimen.
- Patients with a new diagnosis as per inclusion criteria 2, but for whom standard induction chemotherapy would be expected to be well tolerated and a preferred option in the opinion of the principal investigator.
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- Patients with relapsed AML, but for whom a suitable donor of stem cells exists and in whom high-dose chemotherapy with hematopoietic stem cell transplant is felt to be a better immediate alternative.
- Patients with any clinically significant abnormality in screening blood chemistry, hematology or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention.
- Patients with hypersensitivity to Bortezomib, boron, or mannitol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Kentucky
Lexington, Kentucky, 40536
University of Rochester
Rochester, New York, 14642
About this study
Official title: A Phase I Study Using Bortezomib (Velcade, Formerly Known as PS-341) With Weekly Idarubicin for the Treatment of Elderly (>/= 60 Years) and Relapsed Patients With Acute Myelogenous Leukemia
The purpose of this study is to determine the maximal tolerated dose (MTD) of bortezomib and idarubicin given in combination to newly diagnosed AML patients >60 years or relapsed AML patients.
Another purpose of this study is to determine the dose limiting toxicities associated with bortezomib in combination with idarubicin in newly diagnosed AML patients >60 years or relapsed AML patients.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- Velcade, Idarubicin
- Keywords
- Acute Myelogenous Leukemia, AML, Relapse, Elderly, Velcade, Idarubicin, Bortezomib
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VelcadeDrug
Also called Bortezomib
velcade (4 original dosing levels with 3 modified dosing levels) I.V. on days 1, 4, 8, 11, 15, 18, 22, and 25 for 4 weeks concurrent with the Idarubicin
IdarubicinDrug
I.V., 8, or 10 or 12 mg/m^2 weekly (days 1, 8, 15, and 22) for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 escalation | Experimental | Not described Receives: Drug: Velcade; Drug: Idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of bortezomib & idarubicin given in combination, with idarubicin given once weekly for 4 consecutive weeks & bortezomib given twice weekly over the same time.
Measured: week 4
Dose limiting toxicities associated with bortezomib in combination with idarubicin.
Measured: week 4
Secondary outcomes (5)
Response to the combination of Idarubicin and Bortezomib.
Measured: Days 18 & 50
Pre- & post-treatment inhibition of NF-kB activity in the malignant & normal hematopoietic cell populations.
Measured: 24 hours after the initial dose of Bortezomib
Induction of p53 levels in the malignant cell populations.
Measured: 2 and 24 hours post day +1 Bortezomib
Bortezomib PK when administered to patients with acute leukemia receiving concomitant medications that could lead to drug interactions. In the case of altered pharmacokinetics, a pharmacodynamic assay to check proteasome inhibition may also be applied.
Measured: Days 1, 4, 8, 11, 15
Idarubicin PK in order to observe any alteration in metabolism/elimination of Idarubicin & its active metabolite idarubicinol when it is combined with Bortezomib.
Measured: Days 1, 4, 8, 11, 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2006 (estimated)
- Study startFeb 2004
- Primary completionOct 2008
- Study completionOct 2008
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 Myelogenous 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kentucky
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Dianna Howard, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00382954
- Sponsor's protocol ID
- 03-BMT-145
- Status last verified
- Sep 2010
- First submitted
- 28 Sep 2006
- Last updated
- 29 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Howard DS, Liesveld J, Phillips GL 2nd, Hayslip J, Weiss H, Jordan CT, Guzman ML. A phase I study using bortezomib with weekly idarubicin for treatment of elderly patients with acute myeloid leukemia. Leuk Res. 2013 Nov;37(11):1502-8. doi: 10.1016/j.leukres.2013.09.003. Epub 2013 Sep 8.
PubMed 24075534
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Using Bortezomib (Velcade, Formerly Known as PS-341) With Weekly Idarubicin for the Treatment of Elderly (>/= 60 Years) and Relapsed Patients With Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT00382954
- Acronym / sponsor ID
- 03-BMT-145
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Acute Myelogenous Leukemia, AML, Relapse, Elderly, Velcade, Idarubicin, Bortezomib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- University of KentuckyUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Feb 2004
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 2 Oct 2006 (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 the maximal tolerated dose (MTD) of bortezomib and idarubicin given in combination to newly diagnosed AML patients >60 years or relapsed AML patients.
Another purpose of this study is to determine the dose limiting toxicities associated with bortezomib in combination with idarubicin in newly diagnosed AML patients >60 years or relapsed AML patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1 escalation | Experimental | Drug: Velcade, Drug: Idarubicin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age: > 60 years of age for newly diagnosed/transformed disease; > 18 years of age for relapsed disease.
- AML with or without antecedent hematologic disorder diagnosed by morphologic, histochemical, or cell surface marker criteria - as defined by the WHO classification (17).
- Newly diagnosed, elderly patients who are considered unsuitable for intensive chemotherapy induction -- antecedent hematologic disorders, pre-existing myelodysplasia, trilineage dyspoiesis, unfavorable cytogenetics, or pre-existing comorbidities.
- Untreated conditions meeting criteria the first and third criteria or patients with diagnosis as in criteria 2 who have relapsed after at least one successful induction therapy. (Relapsed patients treated on this protocol will be patients without a suitable donor for transplant or for whom transplant is not an option for other reasons.)
- Karnofsky performance status >60.
Key exclusion criteria (9 listed)
- Patients with acute promyelocytic leukemia. Patients with uncontrolled systemic infection.
- Patients who are known to be HIV seropositive.
- Patients with evidence of CNS leukemia.
- Patients who are pregnant or lactating.
- Patients with primarily refractory disease unresponsive to a standard induction regimen.
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 |
|---|---|---|
| VelcadeAlso: Bortezomibvelcade (4 original dosing levels with 3 modified dosing levels) I.V. on days 1, 4, 8, 11, 15, 18, 22, and 25 for 4 weeks concurrent with the Idarubicin | Drug | Phase 1 escalation |
| IdarubicinI.V., 8, or 10 or 12 mg/m^2 weekly (days 1, 8, 15, and 22) for 4 weeks | Drug | Phase 1 escalation |
Primary outcome
Maximum tolerated dose of bortezomib & idarubicin given in combination, with idarubicin given once weekly for 4 consecutive weeks & bortezomib given twice weekly over the same time.
Time frame: week 4
Dose limiting toxicities associated with bortezomib in combination with idarubicin.
Time frame: week 4
5 secondary outcomes
Response to the combination of Idarubicin and Bortezomib.
Time frame: Days 18 & 50
Pre- & post-treatment inhibition of NF-kB activity in the malignant & normal hematopoietic cell populations.
Time frame: 24 hours after the initial dose of Bortezomib
Induction of p53 levels in the malignant cell populations.
Time frame: 2 and 24 hours post day +1 Bortezomib
Bortezomib PK when administered to patients with acute leukemia receiving concomitant medications that could lead to drug interactions. In the case of altered pharmacokinetics, a pharmacodynamic assay to check proteasome inhibition may also be applied.
Time frame: Days 1, 4, 8, 11, 15
Idarubicin PK in order to observe any alteration in metabolism/elimination of Idarubicin & its active metabolite idarubicinol when it is combined with Bortezomib.
Time frame: Days 1, 4, 8, 11, 15
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 29 Sep 2010.
- Derived from this study: PubMed 24075534Howard DS, Liesveld J, Phillips GL 2nd, Hayslip J, Weiss H, Jordan CT, Guzman ML. A phase I study using bortezomib with weekly idarubicin for treatment of elderly patients with acute myeloid leukemia. Leuk Res. 2013 Nov;37(11):1502-8. doi: 10.1016/j.leukres.2013.09.003. Epub 2013 Sep 8.
- University of Kentucky Markey Cancer Center Clinical Trials ListingLink 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.
Dianna Howard, MD principal investigator
University of Kentucky
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Velcade and Idarubicin in people with Acute Myelogenous Leukemia, run by University of Kentucky at 2 sites in United States.
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 12 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 29 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 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.
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 bortezomib & idarubicin given in combination, with idarubicin given once weekly for 4 consecutive weeks & bortezomib given twice weekly over the same time. (time frame: week 4). 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 NCT00382954, 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 29 Sep 2010.