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

CLL/SLL Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05590702
• Other study ID #: FILObsLLC_FOLLOW
• Status: Recruiting
• Start date: November 11, 2022
• Est. completion date: December 1, 2032

Study information

• Verified date: March 2023
• Source: French Innovative Leukemia Organisation
• Contact: Valérie ROUILLE
• Phone: 04 67 33 26 45
• Email: v.rouille[@]filo-leucemie.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 1, 2032
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• CLL/SLL
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
France	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-Jallieu
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 - CHUGA - Hématologie Clinique	Grenoble
France	GRENOBLE GHM - Institut Daniel Hollard	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 CHU - Hôpital Claude Huriez	Lille
France	LILLE GHICL - Hôpital Saint Vincent de Paul	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	Perigueux - Ch	Périgueux
France	PERPIGNAN - CH St Jean - Hématologie Clinique	Perpignan
France	Bordeaux Pessac	Pessac
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

Sponsors (5)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	AbbVie, AstraZeneca, BeiGene, Janssen-Cilag Ltd.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Representativity of CLL therapies and sequences across	Number of patients who received a particular type of therapy (chemo-immunotherapy, kinase inhibitors targeting the B-cell receptor signaling, B-cell lymphoma 2 inhibitor) at baseline and in relapse and in which sequence	7-year period of time
Secondary	Overall survival	registering cause of death focusing on CLL, infection, Richter's syndrome, immune disorders and secondary malignancies	7 years
Secondary	Long-term toxicity	infection requiring hospitalization, secondary malignancies, cardiac and vascular events	7 years