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Evaluation of a Cardiovascular Active Prevention in Chronic Myeloid Leukemia on the Cardiovascular Morbi-mortality (PALERMO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03746054
Recruitment Status : Not yet recruiting
First Posted : November 19, 2018
Last Update Posted : November 21, 2018
Information provided by (Responsible Party):
University Hospital, Angers

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia (CML) Combination Product: Optimal medical treatment Combination Product: usual clinical practice Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: active prevention
optimal medical treatment
Combination Product: Optimal medical treatment
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

Sham Comparator: usual clinical practice
usual clinical practice in each center
Combination Product: usual clinical practice
usual clinical practice in each center

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults over 18 years
  • CML "Philadelphia chromosome" in chronic phase treated with nilotinib or ponatinib for, in first or second line
  • Life expectancy above 12 months
  • Written informed consent must be obtained prior to protocol-specific procedures
  • Affiliation to a social security category

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03746054

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Contact: HENNI SAMIR, MD, PhD 33(0)241354617
Contact: MARECHAL-GIRAULT STEPHANIE, MSc 33(0)241356208

Sponsors and Collaborators
University Hospital, Angers
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Principal Investigator: HENNI SAMIR, MD, PhD Angers Teaching Hospital

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Responsible Party: University Hospital, Angers Identifier: NCT03746054     History of Changes
Other Study ID Numbers: PHRC-K-2017
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Angers:
Chronic Myeloid Leukemia
Vascular medicine

Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases