Chronic Myeloid Leukemia (CML)Phase 3PALERMONCT03746054
Evaluation of a Cardiovascular Active Prevention in Chronic Myeloid Leukemia on the Cardiovascular Morbi-mortality
A Phase 3 study testing Optimal medical treatment and usual clinical practice in people with Chronic Myeloid Leukemia (CML), run by University Hospital, Angers at 1 site in France.
Trial summary
According to the French National Cancer Institute, 35 000 new hematologic cancers are observed in France representing 10% of the new cancers. Chronic Myeloid Leukemia (CML) is a cancer involving the bone marrow and blood cells, the median age at diagnosis is 53 years in the Western world. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia (CML)
- What is being tested?
- Optimal medical treatment and usual clinical practice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 20 Dec 2019to 16 Apr 2024
- Phase
- Phase 3
- 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
- Adults over 18 years
- CML "Philadelphia chromosome" in chronic phase treated with nilotinib or ponatinib for, in first or second line
- Written informed consent must be obtained prior to protocol-specific procedures
- Affiliation to a social security category
Who cannot join
- Revascularization already decided and scheduled
- Life threatening disease
- Recent history of myocardial infarction or stroke
- Unstable angina
- Hypotension (Blood pressure < 90/50mmHg)
- Pregnancy and lactation
Show all 26Show fewer
- Women of childbearing potential not using appropriate contraceptive measures
- Contraindication for statin
- Contraindication for aspirin
- Contraindication for ACEi or AT2 antagonists treatment
- Known hypersensitivity to rosuvastatin or fluvastatin, other ingredients in the product
- Known hypersensitivity to aspirin, other ingredients in the product, other salicylates or non-steroidal anti-inflammatory drugs
- Known hypersensitivity to ACEi or AT2 antagonists treatment, other ingredients in the product
- Hereditary or idiopathic angioedema ; or history of angioedema
- Hyperaldosteronism
- Active liver disease, or unexplained, persistent elevations in serum transaminases
- Severe renal impairment (creatinine clearance <30 ml/min)
- Myopathy
- Concomitant cyclosporine treatment
- History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy
- Severe heart failure
- Concurrent severe diseases which exclude the administration of therapy
- Patients under reinforced protection, deprived of liberty by judicial or administrative decision, hospitalized without consent or admitted to a health or social establishment for purposes other than research
- Absence of affiliation to a social security agency
- Inability to understand the instructions or objectives of the study
- Absence of signed informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Study, Randomized, Multicenter, Evaluating the Efficacy of a Cardiovascular Active Prevention Vs Usual Clinical Practice, on the Morbi-mortality Decrease in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitor
According to the French National Cancer Institute, 35 000 new hematologic cancers are observed in France representing 10% of the new cancers. Chronic Myeloid Leukemia (CML) is a cancer involving the bone marrow and blood cells, the median age at diagnosis is 53 years in the Western world. The prognosis is worse than many other cancers with net survival at 5 years of 26%.
Since the approval of imatinib, additional tyrosine kinase inhibitors (TKIs) have been approved by the European Medicine Agency, including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib. Despite their effect on the evolution of CML, there is increasing of cardiovascular toxicities which can impact patient morbidity and mortality. The majority of the cardiovascular toxicities are associated with the second- and third-generation TKIs. Nilotinib and ponatinib cardiovascular toxicity including arterial and venous thromboembolism has decrease the benefit/risk ratio, 10% of patients treated with nilotinib 300 mg twice daily and 15.9% treated with 400 mg twice daily experienced a vascular complication including myocardial infarction /ischemic heart disease, cerebrovascular accidents, or peripheral arterial disease. Regarding ponatinib, serious arterial occlusive adverse reactions occurred in 19% of patients.
In an attempt to reduce major adverse cardiovascular events MACE due to nilotinib and ponatinib, currently, then approach is driven by usual clinical practice without any robust published evidence. The investigators aim to perform a national clinical trial, multicenter, prospective, randomized, with two parallel comparative arms: experimental group with cardiovascular active prevention vs non active cardiovascular active prevention based on usual clinical practice. Our hypothesis is that active prevention of cardiovascular toxicities with optimal medical treatment improves the benefit-risk ratio in CML patients. The primary objective is Event Free Survival (EFS) at month 24.
Read the detailed description
At admission eligible patients are proposed to participate. Written consent is signed after complete oral and written explanation of the protocol is signed.
The efficacity of the cardiovascular active prevention will be studied by comparing the rate of Event free Survival between patients in the Experimental Arm Versus usual Clinical practices
The duration of participation for a subject is equal to 2 years
- Conditions
- Chronic Myeloid Leukemia (CML)
- Being tested
- Optimal medical treatment, usual clinical practice
- Keywords
- Blood, Chronic Myeloid Leukemia, Vascular medicine
- 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.
Optimal medical treatmentCombination product
Life style modifications, Monitoring of the risk factors and Optimal medical treatment Lipid-lowering treatment, anti-platelet treatment and ACEi or AT2 antagonists treatment for a total duration of 24 months
usual clinical practiceCombination product
usual clinical practice in each center
| Study group | Role | What they receive |
|---|---|---|
| active prevention | Experimental | optimal medical treatment Receives: Combination Product: Optimal medical treatment |
| usual clinical practice | Sham comparator | usual clinical practice in each center Receives: Combination Product: usual clinical practice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvementof the Event Free Survival (EFS) rate in CML patients with an active and systematic prevention for cardiovascular risk.
The Event Free Survival (EFS) is based on the analysis of the time to an event occurrence.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start20 Dec 2019
- Primary completion16 Apr 2024
- Study completion16 Apr 2024
Why it stopped: Inclusions stopped on 25MAR2022 due to lack of inclusion Last follow-up on 16APR2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid Leukemia (CML)Studies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- HENNI SAMIR, MD, PhD, Principal investigator, Angers Teaching Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03746054
- Sponsor's protocol ID
- PHRC-K-2017
- Acronym
- PALERMO
- Status last verified
- Mar 2024
- First submitted
- 15 Nov 2018
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study, Randomized, Multicenter, Evaluating the Efficacy of a Cardiovascular Active Prevention Vs Usual Clinical Practice, on the Morbi-mortality Decrease in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitor
- ClinicalTrials.gov ID
- NCT03746054
- Acronym / sponsor ID
- PALERMO / PHRC-K-2017
- Conditions
- Chronic Myeloid Leukemia (CML)
- Keywords
- Blood, Chronic Myeloid Leukemia, Vascular medicine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inclusions stopped on 25MAR2022 due to lack of inclusion Last follow-up on 16APR2024
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 20 Dec 2019 (actual)
- Primary completion
- 16 Apr 2024 (actual)
- Study completion
- 16 Apr 2024 (actual)
- First posted
- 19 Nov 2018 (actual)
- 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.
According to the French National Cancer Institute, 35 000 new hematologic cancers are observed in France representing 10% of the new cancers. Chronic Myeloid Leukemia (CML) is a cancer involving the bone marrow and blood cells, the median age at diagnosis is 53 years in the Western world. The prognosis is worse than many other cancers with net survival at 5 years of 26%.
Since the approval of imatinib, additional tyrosine kinase inhibitors (TKIs) have been approved by the European Medicine Agency, including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib. Despite their effect on the evolution of CML, there is increasing of cardiovascular toxicities which can impact patient morbidity and mortality. The majority of the cardiovascular toxicities are associated with the second- and third-generation TKIs. Nilotinib and ponatinib cardiovascular toxicity including arterial and venous thromboembolism has decrease the benefit/risk ratio, 10% of patients treated with nilotinib 300 mg twice daily and 15.9% treated with 400 mg twice daily experienced a vascular complication including myocardial infarction /ischemic heart disease, cerebrovascular accidents, or peripheral arterial disease. Regarding ponatinib, serious arterial occlusive adverse reactions occurred in 19% of patients.
In an attempt to reduce major adverse cardiovascular events MACE due to nilotinib and ponatinib, currently, then approach is driven by usual clinical practice without any robust published evidence. The investigators aim to perform a national clinical trial, multicenter, prospective, randomized, with two parallel comparative arms: experimental group with cardiovascular active prevention vs non active cardiovascular active prevention based on usual clinical practice. Our hypothesis is that active prevention of cardiovascular toxicities with optimal medical treatment improves the benefit-risk ratio in CML patients. The primary objective is Event Free Survival (EFS) at month 24.
Detailed description
At admission eligible patients are proposed to participate. Written consent is signed after complete oral and written explanation of the protocol is signed.
The efficacity of the cardiovascular active prevention will be studied by comparing the rate of Event free Survival between patients in the Experimental Arm Versus usual Clinical practices
The duration of participation for a subject is equal to 2 years
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active prevention | Experimental | Combination Product: Optimal medical treatmentoptimal medical treatment |
| usual clinical practice | Sham comparator | Combination Product: usual clinical practiceusual clinical practice in each center |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults over 18 years
- CML "Philadelphia chromosome" in chronic phase treated with nilotinib or ponatinib for, in first or second line
- Written informed consent must be obtained prior to protocol-specific procedures
- Affiliation to a social security category
Key exclusion criteria (26 listed)
- Revascularization already decided and scheduled
- Life threatening disease
- Recent history of myocardial infarction or stroke
- Unstable angina
- Hypotension (Blood pressure < 90/50mmHg)
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 |
|---|---|---|
| Optimal medical treatmentLife style modifications, Monitoring of the risk factors and Optimal medical treatment Lipid-lowering treatment, anti-platelet treatment and ACEi or AT2 antagonists treatment for a total duration of 24 months | Combination product | active prevention |
| usual clinical practiceusual clinical practice in each center | Combination product | usual clinical practice |
Primary outcome
Improvementof the Event Free Survival (EFS) rate in CML patients with an active and systematic prevention for cardiovascular risk.
Time frame: 24 months
The Event Free Survival (EFS) is based on the analysis of the time to an event occurrence.
Results and safety
The study was stopped early (reason given: Inclusions stopped on 25MAR2022 due to lack of inclusion Last follow-up on 16APR2024). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Individual participant dataSharing planned: No
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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.
HENNI SAMIR, MD, PhD principal investigator
Angers Teaching Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Optimal medical treatment and usual clinical practice in people with Chronic Myeloid Leukemia (CML), run by University Hospital, Angers at 1 site in France.
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 4 inclusion and 26 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 17 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Inclusions stopped on 25MAR2022 due to lack of inclusion Last follow-up on 16APR2024). 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?
Improvementof the Event Free Survival (EFS) rate in CML patients with an active and systematic prevention for cardiovascular risk. (time frame: 24 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 17 Mar 2025.