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

NCT03746054 | Terminated Phase 3 DMC

• 1 other identifier: PHRC-K-2017
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia (CML)

Keywords

Blood; Chronic Myeloid Leukemia; Vascular medicine

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Study Arms (2)

active prevention

EXPERIMENTAL

optimal medical treatment

Combination Product: Optimal medical treatment

usual clinical practice

SHAM COMPARATOR

usual clinical practice in each center

Combination Product: usual clinical practice

Interventions

Optimal medical treatment COMBINATION_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

active prevention

usual clinical practice COMBINATION_PRODUCT

usual clinical practice in each center

usual clinical practice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

CHU

Angers, France

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• HENNI SAMIR, MD, PhD

  Angers Teaching Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 19, 2018
• Study Start: December 20, 2019
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: March 17, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)