Chronic Myelogenous LeukemiaPhase 1NCT01397734
Arsenic Trioxide and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (CML)
A Phase 1 study testing Arsenic trioxide in people with Chronic Myelogenous Leukemia, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
In this research study, the investigators are looking to see whether the combination of arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on chronic myelogenous leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous Leukemia
- What is being tested?
- Arsenic trioxide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to 6 Aug 2018
- 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
- Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by fluorescent In Situ Hybridization (FISH) for BCR/ABL translocation and/or standard cytogenetics analysis.
- Participants may have received prior hydroxyurea but may not be currently being treated with hydroxyurea at the time of study initiation.
- Participants may have received prior TKI therapy, however must be on a stable dose of their current TKI for at least one month prior to enrollment.
- Participants must demonstrate evidence of persistent disease either by cytogenetics/FISH or by PCR for BCR/ABL in the peripheral blood or bone marrow.
- Greater than or equal to 18 years in age. Because little dosing or adverse event data are currently available on the use of Arsenic in participants <18 years of age, children are excluded from this study.
- Life expectancy of greater than 3 months
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- ECOG performance status <2
- Participants must have normal organ and marrow function as defined below:
- Bilirubin ≤ 2.0 mg/dL
- Creatinine ≤ 2 mg/dL
- ALT < 2.5 X institutional upper limit of normal
- AST < 2.5 X institutional upper limit of normal
- WBC > 2.0 K/uL
- Platelets >100K
- Oxygen saturation > 95% on room air
- The effects of Arsenic on the developing human fetus are unknown. For this reason, women of child-bearing potential must have a documented negative pregnancy test; in addition, agreement to use adequate contraception (hormonal or barrier method of birth control; abstinence) must be documented for both women of child-bearing potential and men prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- All patients must demonstrate the ability to understand the investigational nature of this study and must sign a written informed consent document in accordance with institutional and federal guidelines
Who cannot join
- History of acute myocardial infarction, unstable angina, congestive heart failure, or arrhythmia within the last three months
- Participants may not be receiving any other study agent
- Mean QTc> 450 ms at time of screening
- Use of potassium wasting diuretics during study treatment
- Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. The following must be discontinued at least 7 days prior to enrollment to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- Drugs that are highly dependent on CYP3A4 for metabolism and have a narrow therapeutic index (see Appendix A) are allowed but must be used with caution
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Concurrent and or uncontrolled psychiatric or medical condition which may interfere with the study completion.
- Pregnant women are excluded from this study because the risk of Arsenic to a developing fetus is unknown. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Arsenic, breastfeeding should be discontinued if the mother is treated on this clinical trial
- Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TKI therapy and Arsenic. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Targeting of the Leukemia Stem Cell Population With Arsenic Trioxide and Tyrosine Kinase Inhibitors for CML
In this research study, the investigators are looking to see whether the combination of arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on chronic myelogenous leukemia.
- Conditions
- Chronic Myelogenous Leukemia
- Being tested
- Arsenic trioxide
- Keywords
- CML, Chronic myelogenous leukemia, Chronic Myeloid leukemia, Arsenic, Arsenic trioxide, Imatinib, Dasatinib, Nilotinib, TKI, Tyrosine kinase inhibitor
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic trioxideDrug
0.15mg/kg/day Arsenic trioxide given IV on days 1-5 of the cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Patients who are receiving Imatinib as part of their standard of care therapy for CML. Receives: Drug: Arsenic trioxide |
| Cohort 2 | Experimental | Patients who are receiving Dasatinib as part of their standard of care therapy for CML. Receives: Drug: Arsenic trioxide |
| Cohort 3 | Experimental | Patients who are receiving Nilotinib as part of their standard of care therapy for CML. Receives: Drug: Arsenic trioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Toxicity
To assess the safety and toxicity of arsenic in combination with TKI therapy for chronic phase CML patients
Measured: 1, 2, 6, 12 months
Secondary outcomes (2)
Disease Response
To assess disease response after combined therapy arsenic trioxide and imatinib (cohort 1), dasatinib (cohort 2) or nilotinib (cohort 3) by bone marrow cytogenetic assessment and serial BCR-ABL QPCR from peripheral blood and bone marrow measurements. Rates of major and complete cytogenetic and molecular responses will be determined.
Measured: 1, 2, 6, 12 months
PML Expression
To assess whether combined therapy with arsenic and imatinib, dasatinib or nilotinib results in decreased PML expression on the CML stem cell compartment, and decreased capacity of CML stem cells to maintain long term proliferative capacity.
Measured: 1, 6, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study startSep 2011
- Primary completion6 Aug 2018
- Study completion6 Aug 2018
Why it stopped: Lack of enrollment and limited funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Teva Pharmaceuticals USA
- Responsible party
- Principal investigator, David Avigan, MD, Beth Israel Deaconess Medical Center
- Investigators
- David E Avigan, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01397734
- Sponsor's protocol ID
- 11-107
- Status last verified
- Sep 2018
- First submitted
- 18 Jul 2011
- Last updated
- 6 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting of the Leukemia Stem Cell Population With Arsenic Trioxide and Tyrosine Kinase Inhibitors for CML
- ClinicalTrials.gov ID
- NCT01397734
- Acronym / sponsor ID
- 11-107
- Conditions
- Chronic Myelogenous Leukemia
- Keywords
- CML, Chronic myelogenous leukemia, Chronic Myeloid leukemia, Arsenic, Arsenic trioxide, Imatinib, Dasatinib, Nilotinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment and limited funding
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Teva Pharmaceuticals USA
- Study start
- Sep 2011
- Primary completion
- 6 Aug 2018 (actual)
- Study completion
- 6 Aug 2018 (actual)
- First posted
- 20 Jul 2011 (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.
In this research study, the investigators are looking to see whether the combination of arsenic trioxide with a tyrosine kinase inhibitor is safe, and what effects it has on chronic myelogenous leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Arsenic trioxidePatients who are receiving Imatinib as part of their standard of care therapy for CML. |
| Cohort 2 | Experimental | Drug: Arsenic trioxidePatients who are receiving Dasatinib as part of their standard of care therapy for CML. |
| Cohort 3 | Experimental | Drug: Arsenic trioxidePatients who are receiving Nilotinib as part of their standard of care therapy for CML. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Participants must have a diagnosis of chronic myelogenous leukemia as confirmed by fluorescent In Situ Hybridization (FISH) for BCR/ABL translocation and/or standard cytogenetics analysis.
- Participants may have received prior hydroxyurea but may not be currently being treated with hydroxyurea at the time of study initiation.
- Participants may have received prior TKI therapy, however must be on a stable dose of their current TKI for at least one month prior to enrollment.
- Participants must demonstrate evidence of persistent disease either by cytogenetics/FISH or by PCR for BCR/ABL in the peripheral blood or bone marrow.
- Greater than or equal to 18 years in age. Because little dosing or adverse event data are currently available on the use of Arsenic in participants <18 years of age, children are excluded from this study.
Key exclusion criteria (11 listed)
- History of acute myocardial infarction, unstable angina, congestive heart failure, or arrhythmia within the last three months
- Participants may not be receiving any other study agent
- Mean QTc> 450 ms at time of screening
- Use of potassium wasting diuretics during study treatment
- Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. The following must be discontinued at least 7 days prior to enrollment to be eligible: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
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 |
|---|---|---|
| Arsenic trioxide0.15mg/kg/day Arsenic trioxide given IV on days 1-5 of the cycle. | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Toxicity
Time frame: 1, 2, 6, 12 months
To assess the safety and toxicity of arsenic in combination with TKI therapy for chronic phase CML patients
2 secondary outcomes
Disease Response
Time frame: 1, 2, 6, 12 months
PML Expression
Time frame: 1, 6, 12 months
Results and safety
The study was stopped early (reason given: Lack of enrollment and limited funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2018.
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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.
David E Avigan, MD principal investigator
Beth Israel Deaconess 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 study testing Arsenic trioxide in people with Chronic Myelogenous Leukemia, run by Beth Israel Deaconess Medical Center at 1 site 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 17 inclusion and 11 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: stopped early, as of the sponsor's last update on 6 Sep 2018. 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 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 was stopped early (reason given: Lack of enrollment and limited funding). Results are not available in the source record.
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?
Number of Participants with Adverse Events as a Measure of Safety and Toxicity (time frame: 1, 2, 6, 12 months). 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 6 Sep 2018.