French Observational Study of Patients With Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma in Real-World Settings

NCT ID: NCT05590702

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-11-11
• Study Completion Date: 2032-12-01

Brief Summary

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. 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.

We here propose to set a large-scale prospective and non-interventional study including patients with symptomatic CLL/SLL with the aim to evaluate the real-world clinical management of these patients and to identify the impact of treatments and therapeutic trajectories on long-term outcome.

Detailed Description

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

Conditions

CLL/SLL

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

First line therapy

Patient with CLL or SLL requiring a therapeutic strategy according to iwCLL criteria or investigator evaluation will be identified in MCM (multidisciplinary collegial meeting).

Patients will be treated and managed according to the decision of their physicians and the related MDM. No treatment plan is recommended in the setting of this non-interventional study.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18-year old
• CLL or SLL requiring a therapeutic strategy according to iwCLL criteria or investigator evaluation
• Patient requiring therapy for immune events (autoimmune Thrombocytopenia and autoimmune hemolytic anemia) are eligible
• Patients who have been informed verbally and in writing about this study, and who do not object to their data being electronically processed or subjected to data quality control
• All consecutive patients for whom a discussion in the setting of local or regional multidisciplinary collegial meeting (in french : réunion de concertation pluridisciplinaire / RCP) has retained the need for starting a therapeutic strategy (curative or palliative)
• Patients with untreated or previously treated CLL/SLL are both eligible
• Patients enrolled in a clinical trial can be included in this non-interventional cohort study
• Patients requiring therapy for CLL/SLL-associated immune events only are also eligible

Exclusion Criteria

• Patients with no need of therapy
• Patients with asymptomatic Binet A CLL
• Patient with Richter's syndrome at inclusion
• Patient requiring immunoglobulin substitution (with no need of a more specific therapy)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

BeiGene

INDUSTRY

Sponsor Role: collaborator

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

French Innovative Leukemia Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Romain GUIEZE

Role: PRINCIPAL_INVESTIGATOR

French Innovative Leukemia Organisation

Xavier TROUSSARD

Role: STUDY_CHAIR

French Innovative Leukemia Organisation

Locations

AMIENS - CH Amiens Picardie Site Sud

Amiens, , France

Angers Chu

Angers, , France

ANNECY - CH Annecy Genevois

Annecy, , France

ARGENTEUIL - Centre hospitalier Victor Dupouy

Argenteuil, , France

AVIGNON - Centre Hospitalier

Avignon, , France

BESANCON - Hôpital Jean Minjoz

Besançon, , France

BEZIERS - Centre Hospitalier - Hématologie

Béziers, , France

BLOIS CH

Blois, , France

APHP - Hôpital Avicenne

Bobigny, , France

APHP - Hôpital Jean Verdier

Bondy, , France

BOURGOUIN-JALLIEU - CH Pierre Oudot

Bourgoin, , France

BREST - Hôpital Morvan - Hématologie Clinique

Brest, , France

CAEN - IHBN - Hématologie Clinique

Caen, , France

CERGY PONTOISE - CH René Dubos

Cergy-Pontoise, , France

CHAMBERY - CH Métropole Savoie

Chambéry, , France

Clermont-Ferrand - Chu Estaing

Clermont-Ferrand, , France

Corbeil-Essonnes - Chsf

Corbeil-Essonnes, , France

Dijon Chu

Dijon, , France

GRENOBLE GHM - Institut Daniel Hollard

Grenoble, , France

Grenoble - CHUGA - Hématologie Clinique

Grenoble, , France

La Roche Sur Yon - Chd Vendee

La Roche-sur-Yon, , France

Le Mans CH

Le Mans, , France

LENS - GHT Artois

Lens, , France

LIBOURNE - Hôpital Robert Boulin

Libourne, , France

LILLE GHICL - Hôpital Saint Vincent de Paul

Lille, , France

LILLE CHU - Hôpital Claude Huriez

Lille, , France

LIMOGES - CHU Dupuytren 1

Limoges, , France

LYON-Centre Léon Bérard

Lyon, , France

METZ-THIONVILLE CHR- Hôpital de Mercy

Metz, , France

MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, , France

MORLAIX - CH des pays de Morlaix

Morlaix, , France

Mulhouse - Ghrmsa

Mulhouse, , France

NANTES - Hôpital Hôtel Dieu - Hématologie Clinique

Nantes, , France

NIMES - CHU Caremeau

Nîmes, , France

ORLEANS - CHR - Hématologie

Orléans, , France

APHP - HOPITAL COCHIN - Hématologie

Paris, , France

APHP - Hôpital Pitié Salpêtrière - Hématologie

Paris, , France

PERPIGNAN - CH St Jean - Hématologie Clinique

Perpignan, , France

Bordeaux Pessac

Pessac, , France

Perigueux - Ch

Périgueux, , France

LYON HCL - CH Lyon Sud

Pierre-Bénite, , France

QUIMPER - CH de Cornouaille

Quimper, , France

Reims Chu

Reims, , France

RENNES - CHU Pontchaillou - Hématologie Clinique

Rennes, , France

RENNES - Hôpital Pontchaillou - Hématologie

Rennes, , France

ROUEN - Centre Henri Becquerel - Service Hématologie Clinique

Rouen, , France

SAINT-BRIEUC - Hôpila Yves Le Foll

Saint-Brieuc, , France

La Reunion - Gh Site Sud

Saint-Pierre, , France

ST ETIENNE - CHU et Institut De Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Strasbourg - Icans

Strasbourg, , France

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, , France

TOURS - Hôpital Bretonneau

Tours, , France

Troyes Ch

Troyes, , France

NANCY - CHU Brabois

Vandœuvre-lès-Nancy, , France

Vannes - Chba

Vannes, , France

VERSAILLES - Hôpital André Mignot

Versailles, , France

Villejuif Igr

Villejuif, , France

Countries

France

Other Identifiers

FILObsLLC_FOLLOW

Identifier Type: -

Identifier Source: org_study_id