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

University Hospital, Angers

Status and phase

Terminated

Phase 3

Conditions

Chronic Myeloid Leukemia (CML)

Treatments

Combination Product: Optimal medical treatment

Combination Product: usual clinical practice

Study type

Interventional

Funder types

Other

Identifiers

NCT03746054

PHRC-K-2017

Details and patient eligibility

About

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.

Full 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

Enrollment

80 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

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