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

Sponsor

French Innovative Leukemia Organisation (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05590702

Collaborator

AbbVie (Industry), AstraZeneca (Industry), BeiGene (Industry), Janssen-Cilag Ltd. (Industry)

1,000

Enrollment

Locations

121.2

Anticipated Duration (Months)

17.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
CLL/SLL	Drug: First line therapy

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.

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

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Oct 25, 2022

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Dec 1, 2032

Outcome Measures

Primary Outcome Measures

Representativity of CLL therapies and sequences across [7-year period of time]
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

Secondary Outcome Measures

Overall survival [7 years]
registering cause of death focusing on CLL, infection, Richter's syndrome, immune disorders and secondary malignancies
Long-term toxicity [7 years]
infection requiring hospitalization, secondary malignancies, cardiac and vascular events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	AMIENS - CH Amiens Picardie Site Sud	Amiens	France	80054
2	Angers Chu	Angers	France	49933
3	ANNECY - CH Annecy Genevois	Annecy	France	74374
4	ARGENTEUIL - Centre hospitalier Victor Dupouy	Argenteuil	France
5	AVIGNON - Centre Hospitalier	Avignon	France	84000
6	BESANCON - Hôpital Jean Minjoz	Besançon	France	25000
7	BLOIS CH	Blois	France	41000
8	APHP - Hôpital Avicenne	Bobigny	France
9	APHP - Hôpital Jean Verdier	Bondy	France	93140
10	BOURGOUIN-JALLIEU - CH Pierre Oudot	Bourgoin-Jallieu	France	38300
11	BREST - Hôpital Morvan - Hématologie Clinique	Brest	France	29609
12	BEZIERS - Centre Hospitalier - Hématologie	Béziers	France	34500
13	CAEN - IHBN - Hématologie Clinique	Caen	France	14033
14	CERGY PONTOISE - CH René Dubos	Cergy-Pontoise	France
15	CHAMBERY - CH Métropole Savoie	Chambéry	France	73000
16	Clermont-Ferrand - Chu Estaing	Clermont-Ferrand	France	63000
17	Corbeil-Essonnes - Chsf	Corbeil-Essonnes	France
18	Dijon Chu	Dijon	France	21000
19	GRENOBLE GHM - Institut Daniel Hollard	Grenoble	France	38028
20	Grenoble - CHUGA - Hématologie Clinique	Grenoble	France	38043
21	La Roche Sur Yon - Chd Vendee	La Roche-sur-Yon	France	85925
22	Le Mans CH	Le Mans	France
23	LENS - GHT Artois	Lens	France	62300
24	LIBOURNE - Hôpital Robert Boulin	Libourne	France	33505
25	LILLE GHICL - Hôpital Saint Vincent de Paul	Lille	France	59000
26	LILLE CHU - Hôpital Claude Huriez	Lille	France	59037
27	LIMOGES - CHU Dupuytren 1	Limoges	France	87042
28	LYON-Centre Léon Bérard	Lyon	France	69008
29	METZ-THIONVILLE CHR- Hôpital de Mercy	Metz	France
30	MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique	Montpellier	France	34295
31	MORLAIX - CH des pays de Morlaix	Morlaix	France	29672
32	Mulhouse - Ghrmsa	Mulhouse	France	68100
33	NANTES - Hôpital Hôtel Dieu - Hématologie Clinique	Nantes	France	44093
34	NIMES - CHU Caremeau	Nîmes	France	30029
35	ORLEANS - CHR - Hématologie	Orléans	France	44100
36	APHP - HOPITAL COCHIN - Hématologie	Paris	France	75014
37	APHP - Hôpital Pitié Salpêtrière - Hématologie	Paris	France	75651
38	PERPIGNAN - CH St Jean - Hématologie Clinique	Perpignan	France	66000
39	Bordeaux Pessac	Pessac	France	33604
40	LYON HCL - CH Lyon Sud	Pierre-Bénite	France	69036
41	Perigueux - Ch	Périgueux	France	24000
42	QUIMPER - CH de Cornouaille	Quimper	France	29000
43	Reims Chu	Reims	France	51092
44	RENNES - CHU Pontchaillou - Hématologie Clinique	Rennes	France	35033
45	RENNES - Hôpital Pontchaillou - Hématologie	Rennes	France	35033
46	ROUEN - Centre Henri Becquerel - Service Hématologie Clinique	Rouen	France	76038
47	SAINT-BRIEUC - Hôpila Yves Le Foll	Saint-Brieuc	France	22027
48	La Reunion - Gh Site Sud	Saint-pierre	France
49	ST ETIENNE - CHU et Institut De Cancérologie Lucien Neuwirth	Saint-Priest-en-Jarez	France
50	Strasbourg - Icans	Strasbourg	France	67033
51	Toulouse - IUCT Oncopole - Service d'Hématologie	Toulouse	France	31059
52	TOURS - Hôpital Bretonneau	Tours	France	37000
53	Troyes Ch	Troyes	France
54	NANCY - CHU Brabois	Vandœuvre-lès-Nancy	France	54500
55	NANCY - CHU de Brabois	Vandœuvre-lès-Nancy	France	54500
56	Vannes - Chba	Vannes	France
57	VERSAILLES - Hôpital André Mignot	Versailles	France
58	Villejuif Igr	Villejuif	France

Sponsors and Collaborators

French Innovative Leukemia Organisation
AbbVie
AstraZeneca
BeiGene
Janssen-Cilag Ltd.

Investigators

Principal Investigator: Romain GUIEZE, French Innovative Leukemia Organisation
Study Chair: Xavier TROUSSARD, French Innovative Leukemia Organisation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

French Innovative Leukemia Organisation

ClinicalTrials.gov Identifier:

NCT05590702

Other Study ID Numbers:

FILObsLLC_FOLLOW

First Posted:

Oct 21, 2022

Last Update Posted:

Oct 25, 2022

Last Verified:

Oct 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Oct 25, 2022