Étrelles, France
Comparison of Visual Outcomes After Implantation of the Synthesis Plus and Synthesis Plus Toric
Phase
N/ASpan
160 weeksSponsor
Cutting Edge SASPerpignan
Recruiting
French Observational Study of Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in Real-World Settings
Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in the Western World. The disease is characterized by the accumulation and proliferation of mature, monoclonal, CD5+ B-cells with specific immunophenotype in the peripheral blood (above 5x109/L), bone marrow and secondary lymphoid organs. Small lymphocytic leukemia (SLL) is characterized by similar tumor cells but without increased lymphocyte count. In Europe, CLL has been identified as the second most frequent hematological malignancies after multiple myeloma (Eurocare 5 study) and its standardized incidence in the world has been estimated to be 4/100000 person-years for men and 2.1/100000 person-years for women. In France, 4674 new cases have been observed in 2018 (FRANCIM). A proportion of patients can initially be monitored only while others with symptomatic disease at diagnosis or during follow-up require therapies. The management of these patients have considerably changed over the last decade. Indeed, beyond chemo-immunotherapy, multiple targeted therapies have been approved on the basis of phase 2 and randomized phase 3 clinical trials and have subsequently been used in daily practice. The management of patients with SLL is similar to that of those with CLL. In addition to therapeutic advances, the advent of new sequencing technologies has also identified CLL genetic features that are now being incorporated in patient routine evaluation. Conventional chemo-immunotherapy (CIT) has been the long-standing option for CLL patient without TP53 disruption and different regimens have emerged depending on patient comorbidities (fludarabine-cyclophosphamide-rituximab, FCR; bendamustin-rituximab, BR; GA101-chloraminophene, G-CLB). These regimens fail to be effective in patients with TP53 disruption and alternative strategies are proposed for them. The CLL therapeutic panel is now enriched by oral kinase inhibitors targeting the B-cell receptor signaling. The Bruton's tyrosine kinase inhibitors (BTKi) have been shown to provide prolonged response, even in cases where CIT usually failed, such as patients harboring TP53 disruption. In relapsed/refractory patients, median PFS with the BTKi ibrutinib is 44 months. In the frontline setting, ibrutinib has recently been shown to result in superior PFS and less infectious complications than standard CIT regimens. The advent of the BCL2 (B-cell lymphoma 2) inhibitor venetoclax has recently added another option for the treatment of CLL patients. BCL2 is an antiapoptotic molecule governing mitochondrial apoptosis and is strongly expressed in CLL cells. Inhibiting BCL2 with venetoclax as monotherapy led to 79% response rate in the relapse/refractory setting. Combining venetoclax to rituximab demonstrated better PFS than bendamustine-rituximab in relapsed/refractory patients. However, these treatment approaches also come with new challenges that are difficult to-address in phase 3 clinical trials and that deserve larger scale studies and longer follow-up. The emergence of drug resistance, the changes of safety profiles to deal with in routine practice and the observance of these orally administered drugs are emerging as new concerns. How these compounds change the incidence of typical CLL complication such as Richter transformation, immune cytopenias and infections remains to be determined. A growing body of concerns is also raising regarding the unlimited administration of some of this the compounds (costs, resistance, tolerance). Finally, the optimal order of use of these drugs is unknown. The advent of the BCL2 (B-cell lymphoma 2) inhibitor venetoclax has recently added another option for the treatment of CLL patients 11,12. BCL2 is an antiapoptotic molecule governing mitochondrial apoptosis and is strongly expressed in CLL cells. Inhibiting BCL2 with venetoclax as monotherapy led to 79% response rate in the relapse/refractory setting. Combining venetoclax to rituximab demonstrated better PFS than bendamustine-rituximab in relapsed/refractory patients12. However, these treatment approaches also come with new challenges that are difficult to-address in phase 3 clinical trials and that deserve larger scale studies and longer follow-up. The emergence of drug resistance, the changes of safety profiles to deal with in routine practice and the observance of these orally administered drugs are emerging as new concerns. How these compounds change the incidence of typical CLL complication such as Richter transformation, immune cytopenias and infections remains to be determined. A growing body of concerns is also raising regarding the unlimited administration of some of this the compounds (costs, resistance, tolerance). Finally, the optimal order of use of these drugs is unknown. Primary objective : Setting a prospective cohort of real-world CLL/SLL patients with symptomatic disease in order to evaluate medical practices and their change and representativity over time. Secondary objectives : Overall survival and long-term toxicity, Response and PFS at each line of therapy, Impact of therapeutic trajectories on patient outcome, Representativity of the studied population
Phase
N/ASpan
525 weeksSponsor
French Innovative Leukemia OrganisationPerpignan
Recruiting
Transplantation After Complete Response In Patients With T-cell Lymphoma
Phase
N/ASpan
296 weeksSponsor
Hospices Civils de LyonPerpignan
Recruiting
Validation of Blood Biomarkers for Alzheimer's Disease
Rationale of the project: Recent progress in the biological diagnosis of Alzheimer's disease (AD) is considerable, with the possibility, thanks in particular to ultra-sensitive tests, of having relevant blood biomarkers. These biomarkers, mainly represented by amyloid peptides, tau proteins and neurofilaments, make it possible to consider a stratification of patients according to different classifications, including the ATN scale. Their diagnostic value has been mainly tested on retrospective samples and it is now essential to use them prospectively to confront them with pre-analytical and analytical variability. It is also important to position them in relation to CSF analysis and AD management, from risk assessment, diagnosis, to therapeutic strategies. Main objective: To evaluate, in a prospective consecutive enrollment clinical trial, the diagnostic performance (sensitivity, specificity) of blood biomarkers for Alzheimer's disease. Secondary objectives: - Interest of blood biomarkers for detection of normal/pathological CSF profiles. - Interest of blood biomarkers for other disease including, amyloid angiopathy, frontotemporal dementia (FTD) or lewy body disease (LBD). Methodology: The investigator's laboratory daily receives CSF samples from regional "memory clinics" (mainly from Montpellier, Nîmes, Perpignan) for Aß40, Aß42, t-Tau and p-Tau(181) assays. The results of these tests performed weekly on an automated platform are used by neurologists for the diagnosis of AD. In this non-interventional multi-center clinical trial, with the informed consent of patients, one tube of plasma in addition to CSF is collected. In parallel with the CSF, amyloid peptides and plasma p-Tau is measured. The ApoE4 status will also be determined using MS as previously published by the investigator's group. Plasma biomarkers will then be combined to confirm the presence of AD, as has already been done on retrospective samples by the investigator's laboratory and others. Considering a disease prevalence rate of 20% in the screened population, and to reach a sensitivity of 80% and a specificity close to 90%, it is necessary to include a total of 311 patients in order to obtain an estimate of sensitivity and specificity with a 95% accuracy of +/- 10%. The lost to follow-up rate of about 10% requires the enrollment of 342 patients. The diagnostic performance of this profile will be compared to that of CSF, as well as to the diagnosis assessed by a multidisciplinary team one year after sampling. Expected benefit: The confirmation that blood biomarkers of AD achieve satisfactory diagnostic performance in a clinical setting allows them to be considered in routine use, as a less invasive method, thus with greater acceptance and also the possibility of longitudinal use. The benefit also lies in the evaluation of the interest of supplemental biomarkers such as NfL, for related diseases.
Phase
N/ASpan
110 weeksSponsor
University Hospital, MontpellierPerpignan, Occitanie
Recruiting
Oxygen Therapy Remote Monitoring in COPD Patients.
The observational study consists in collecting physiological data (cardiorespiratory and physical activity) and use of the oxygen therapy device in real life during the first months after the initiation of treatment. For this purpose, two connected medical devices will be provided to each patient during 2 periods of 2 weeks (weeks 6 to 8 then weeks 12 to 14 after the initiation of oxygen therapy). The devices are: 1/ a connected watch that continuously measures vital parameters (heart rate and blood oxygen saturation), and physical activity parameters (no. of steps, distance, duration of effort), and 2/ a Teleox device that remotely monitors patients equipped with an oxygen source (it measures the oxygen flow rate requested by the patient, the duration of use of the oxygen source, and the breathing rate). Study design: a cohort of 250 patients with COPD newly initiated a long term oxygen therapy will be enrolled in the study and follow-up over 6 months. Data will be collected by lung specialists and home health care provider teams at 2 months, 3.5 months and 6 months post-initiation of oxygen therapy.
Phase
N/ASpan
105 weeksSponsor
VivisolPerpignan
Recruiting
PFO Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Aged 60 to 80 Years
The CLOSE trial (NCT00562289, NEJM 2017) has unambiguously demonstrated the superiority of patent foramen ovale (PFO) closure over antiplatelet therapy alone in patients aged up to 60 years with a PFO associated with an atrial septal aneurysm (ASA) or a large right-to-left shunt (so-called "high-risk PFO"), and an otherwise unexplained ischemic stroke. Oral anticoagulant therapy is also a logical approach assuming that PFO-related strokes are due to paradoxical embolism which implies a venous source of embolism, or to direct embolization of a thrombus formed at the atrial level. The CLOSE trial also suggested that oral anticoagulants might reduce stroke recurrence compared to aspirin. There is accumulating evidence that presence of a PFO is significantly associated with cryptogenic stroke in patients over 60 years. Cryptogenic ischemic strokes represent about one third of all ischemic strokes in patients older than 60 years. However, the optimal therapeutic strategy in patients older than 60 years with a PFO and an otherwise unexplained ischemic stroke is unknown, because these patients were excluded from randomized trials. The hypothesis tested in this trial is that transcatheter PFO closure plus long-term antiplatelet therapy is superior to antiplatelet therapy alone and that oral anticoagulant therapy is superior to antiplatelet therapy to prevent recurrent stroke in patients aged 60 to 80 years who have a high-risk PFO and a recent otherwise unexplained ischemic stroke.
Phase
3Span
418 weeksSponsor
Assistance Publique - Hôpitaux de ParisPerpignan
Recruiting
A Clinical-biological Prospective Cohort of Patients With BRAFV600E-mutated Metastatic Colorectal Cancer
Despite substantial progress made in the first- and second line mCRC settings, there are still unmet clinical needs for patients harboring BRAFV600E mutations, especially those with microsatellite stability (MSS) / proficient mismatch repair (pMMR) tumor. The overall survival and access to different treatment in the real-life setting are unknown. Moreover, patient prognosis remains poor and therapeutic resistance to combinations with BRAF inhibitors, is at present, nearly universal. Therefore, it seems essential to prospectively collect clinical and biological data about this rare mCRC subtype. These data will allow us to improve knowledge and to identify clinical and biological factors that could drive therapeutic decisions, predict resistance to treatments, and that are prognostic for survival. In this context, we designed this large, prospective, cohort study to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with BRAFV600E mCRC. This collection of clinical and biological data (tumor tissue and blood samples) will allow us to identify predictive and prognostic biomarkers with several research work packages planned: i. To evaluate the circulating tumor DNA (ctDNA) during the metastatic first-, second-, and third-line treatment to: - Evaluate its positive and negative predictive value. - Identify molecular alterations preceding and explaining clinical resistance during BRAF/EGFR inhibition therapy and immunotherapy. ii. To evaluate BRAFV600E mCRC immune environment both at the tumor and blood level (immunomonitoring). iii. To study specific the dMMR/MSI BRAFV600E subgroup. Furthermore, the data collected will describe the therapeutic management of BRAFV600E mCRC patients in the routine-practice setting which will bring very useful data. The results of the COBRAF study could lay the groundwork to better understand BRAFV600E mCRC and to identify prognostic and predictive biomarkers helping the development of new therapeutic approaches in this population.
Phase
N/ASpan
262 weeksSponsor
UNICANCERPerpignan
Recruiting
Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure
Atrial fibrillation (AF) is the most common heart rhythm disorder. It is the result of uncoordinated action of the atrial myocardial cells, causing rapid and irregular contraction of the heart's atria. The AF prevalence in adults is currently estimated to be between 2% and 4% and is expected to increase by a factor of 2.3 in the next few years, due to the increased longevity of the general population and the increased search for undiagnosed AF. Increased age is an important risk factor for AF, but other increased comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic renal failure, obesity, and obstructive sleep apnoea syndrome, are also important; modifiable risk factors contribute strongly to the development and progression of AF (ESC Guideline, 2020). The European Society of Cardiology (ESC) recommended pulmonary vein isolation (PVI) (Class IA) as first-line ablative strategy for persistent AF (Class IA) (ESC Guideline, 2020). However, PVI alone is only effective in treating about 40% to 60% of patients with persistent AF in the general population (unselected). If we apply this strategy to all patients (PVI alone), we accept to re-do ablative procedure in up to 60% of patients. The second feasible strategy is to treat patients with persistent AF by PVI combined with substrate modulation (ESC Class IIb). This strategy, when done well, by creating irreversible lesions (Marshall-PLAN) can effectively treat 70% to 80% of AF patients. But this implies that the investigator will be doing unnecessary substrate modulation in up to 40% of patients, which can lead to increased risks associated with the ablative procedure, longer procedure times, multiple lesions, etc… In addition, incorrect or incomplete substrate modulation is pro-arrhythmic and leads to recurrences in the form of left atrial flutters, tolerance of which, is generally poor. Both ablative strategies have been widely validated in large numbers of published studies. The problem is to know when and for which patients to apply one or the other of the two strategies. Electric cardioversion could help in selecting the most appropriate strategy.
Phase
N/ASpan
241 weeksSponsor
ElsanPerpignan
Recruiting
Safety and Performance Assessment of the SYMBOL Range of Medical Devices in Patients Underlying Total Hip Arthroplasty
Phase
N/ASpan
680 weeksSponsor
Dedienne Sante S.A.S.Perpignan
Recruiting
AVAJAK: Apixaban/Rivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms
Phase
3Span
261 weeksSponsor
University Hospital, BrestPerpignan
Recruiting