Active clinical trials for "Leukemia, Myelogenous, Chronic, BCR-ABL Positive"

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.

Rationale The pharmacokinetics of imatinib and nilotinib, two BCR/Abl tyrosine-kinase inhibitors (TKI), is variable among patients suffering from chronic myeloid leukemia (CML). Transmembrane transporters may play a pivotal role in interindividual variability in TKI disposition. Furthermore, minimum plasma concentrations (Cmin) higher than 1 mg/L could be associated with a higher likelihood of molecular and cytogenetic responses. The TIKlet study is aimed at evaluating correlations among the pharmacogenetics, pharmacokinetics and treatment efficacy/tolerability of imatinib and nilotinib in CML patients. 1. PATIENTS AND METHODS 1.1. Patients Patients affected by CML will be enrolled after the informed consent will be signed, according to the following inclusion criteria: patients of both sexes, age between 18 and 80 years, treated with imatinib or nilotinib, included in follow-up activities at the participating Hematology Divisions, able to give informed consent, with a proved compliance with the scheduled treatment. The administration of other drugs will be allowed, being known the dose and duration of treatment, as well as smoking and herbal products. Alterations in organ functions or physicochemical exams, body mass index >28 do not represent exclusion criteria. 1.2. Enrollment and follow-up visits During enrollment visit: patients will be informed about the study, their signed informed consent form will be collected and an individual alphanumeric code will be assigned. Patients' data will be recorded within the individual case report form (CRF) and a blood sample will be obtained. At follow-up visits, a blood sample will be collected for therapeutic drug monitoring (TDM) and patients' CRF will be updated. 1.3. Blood samples After centrifugation, the resulting plasma will be collected for TDM. During the enrollment visit, an aliquot of whole blood will be collected for molecular analyses. 1.4 Laboratory analyses TDM will be performed by high-performance liquid chromatography systems, then results will be evaluated by a population pharmacokinetic analysis. Single nucleotide polymorphisms will be investigated in the following genes: ABCB1, ABCG2, hOCT1, OCTN1, OATP1A2. Finally, response to drugs, in terms of Major Molecular Response (MMR) and Complete Cytogenetic Response (CCyR), and tolerability will be evaluated. Any possible correlation among drug disposition, pharmacogenetics and treatment effects will be analyzed.

In this study researchers propose to do a chart review of all patients that are treated outside of a clinical trial with imatinib, dasatinib, nilotinib, or any other tyrosine kinase inhibitor that becomes FDA approved for the managements of CML that come to MDACC for a second opinion. This is an important population of patients that differs in their management from patients treated in clinical trials for several reasons including but not limited to: It represents a very large patient population receiving standard-dose therapy with TKI. We estimate that we have evaluated over 300 patients that fall in this category. The follow-up for patients in the largest trial using standard-dose imatinib (the IRIS trial, with 553 patients in treated with imatinib) has been limited after the first 12 months. For example, the rate of molecular responses after the first 12 months of therapy was not obtained as samples stopped being collected at that time point. Registration studies for dasatinib and nilotinib have similar limitations with limited follow-up and available information coming only from databases from the sponsors to which there is limited access to investigate dosing, chronic toxicities, second malignancies and other important aspects of therapy. Patients who are or become pregnant during therapy with TKI have not been eligible for clinical trials with TKI or had to be taken off study. Thus, there is no information on the effect of TKI on imatinib on pregnancy and conception. We have followed several such patients at MDACC. This is a patient population that follows therapy mostly as directed by their local oncologists. This is frequently less stringently adhered to the recommended guidelines for TKI therapy, with more frequent treatment interruptions, and frequently using suboptimal doses of imatinib (i.e., less than 300mg daily). The effect of these treatment interruptions and suboptimal dosing on response and development of resistance is unclear. Researchers plan to conduct a chart review of these patients to study their treatment course before their initial evaluation at MDACC, and between and during visits to MDACC.

This study is a prospective, open-label, multi-center, non-comparative, observational study to assess safety and effectiveness of Asciminib in the real-world clinical setting in Korean Chronic myeloid leukemia (CML) patients.

The objective of this study is to improve medication, symptom, and disease management of patients with hematological malignancies and multiple chronic conditions (2 or more conditions in addition to cancer) through care coordination between pharmacists working in oncology practices and those working in primary care or community practices (Pharmacists Coordinated care Oncology Model [PCOM]). This is a pilot study in which the investigators will examine the association between outcome measures, but the study design and sample size are insufficient to quantify the impact of OAA initiation or OAA adherence on adherence to chronic medications. This pilot study and data analyses are being done in preparation for a larger, controlled study.

The ultimate goal of CML treatment is to improve survival, including overall survival (OS), progression-free survival (PFS), event-free survival (EFS), and treatment-free remission (TFR). TFR is a new therapeutic goal for chronic myeloid leukemia in chronic phase (CML-CP). In ENESTnd and DASISION trials, both nilotinib and dasatinib achieved DMR more effectively than imatinib. In the guidelines for diagnosis and treatment of chronic myeloid leukemia in China (2020 edition), flumatinib has been recommended as an appropriate first-line treatment for newly diagnosed chronic phase chronic myeloid leukemia (CML-CP) patients. There is no doubt that the second-generation TKIs show great advantages in deep molecular response, which further increases the possibility of achieving treatment-free remission. However, there is no direct comparative study to determine which TKI is better for de novo CML-CP. Thus, we conducted a multi-center, open-lable and real world study to compare the efficacy and safety between flumatinib and nilotinib.

The purpose of this single-arm, open-label, dose escalation + cohort expansion study is to evaluate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-678 in Chronic Myelogenous Leukemia patients who had failure with or are intolerant to TKI treatments.

The objective of this study is to acquire more information about what we are doing during pregnancy in CML patients, in order to possibly establish in the future a consensus on the management of patients receiving TKIs who wants to father a child or become/are pregnant.

The mandate of this MPN registry is to collect clinical information, including molecular results, from consenting patients with a variety of MPNs at different time points during the course of their disease.

To provide the IRB approved mechanism for the prospective collection, analysis and reporting of data on patients who are undergoing either an autologous or allogeneic hematopoietic stem cell transplant for a disease in which a research question is not being addressed and for which peer reviewed, published data have demonstrated efficacy for this treatment approach.