Clinical trial NCT01313611: BRIEF Bendamustine and Rituximab In Elderly Follicular
Official title: BRIEF: Bendamustine and Rituximab In Elderly Follicular: A Multicentric Phase II Study Evaluating the Benefit of a Short Induction Treatment by Bendamustine and Rituximab Followed by Maintenance Therapy With Rituximab In Elderly (≥ 60 Years Old) Patients With Untreated Follicular Lymphoma Patients, With an Intermediate or High FLIPI Score
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Follicular Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2011-03-14
Enrollment: 62
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the complete response rate after a short induction treatment with rituximab (375mg/m2)and bendamustine (90mg/m2)in In Elderly (≥ 60 years old) patients with untreated Follicular lymphoma, with an intermediate or high FLIPI score and without high tumor burden.

This short induction is followed by a rituximab (375mg/m2)maintenance/ Induction schedule:Rituximab+Bendamustine on Day 1, Bendamustine on Day 2, Rituximab on Day 8, Rituximab on Day 15, rituximab on day 22, Bendamustine on Day 29, Bendamustine on Day 30 Maintenance schedule: 12 infusions of rituximab, each 8 weeks


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed follicular lymphoma CD20+, all grades except the grade 3b with a lymph node biopsy performed within 6 months before study entry and with material available for central review
* A minimal initial immunology is required, including : CD20, bcl-2, CD10 and CD5
* Age must be ≥ 60 years
* Patients not previously treated
* Patients with an intermediate or high risk FLIPI score requiring 2 or more of the following adverse prognostic factors:

  1. Age \>60 ans
  2. Ann Arbor Stage (III-IV vs. I-II)
  3. Hemoglobin level ( \< 12g/dL vs. ≥ 12 g/dL)
  4. Number of nodal areas (\< 5 vs. ≥ 5) (Note: LDH should not be considered as an adverse prognostic factor in this study since it is considered as high tumor burden in the GELF criteria)
* Low burden disease at study entry according to the GELF criteria
* Patients with at least one measurable site of disease: patients with only blood or marrow or splenic infiltration are excluded
* Performance status ≤ 2 on the ECOG scale
* Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) including:
* Hemoglobin ≥ 8.0 g/dL (5.0 mmol/L)
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Adequate renal function: calculated creatinine clearance \> 50 ml/min (according to MDRD method) unless these abnormalities are related to lymphoma
* Adequate hepatic function: Total bilirubin \< 2.0 mg/dl (34 µmol/L), AST (SGOT) and ALT (SGPT) ≤ 2.5 x the upper limit of normal unless these abnormalities are related to lymphoma
* Adequate cardiac function: LEVF ≥ 50% calculated by echocardiography or scintigraphy
* Having previously signed a written informed consent

Exclusion Criteria:

* Other histological types of lymphoma than follicular lymphoma
* Grade 3b follicular lymphoma
* Patients previously on watch and wait since more than 6 months from diagnosis
* Patients previously treated for lymphoma, except splenectomy
* Patients with low FLIPI score (0 or 1 adverse prognostic factors not considering elevated LDH)
* Bulky disease at study entry according to the GELF criteria
* Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis)
* Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer or previous cancer in CR without any treatment in the last 5 years
* Positive HIV, HBV (anti-HBc positivity) and HCV serologies before inclusion
* Poor Performance status \> 2 on the ECOG scale
* Known contra-indication to study product
* Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
* Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent.

Primary outcomes:
measure: Complete response rate according to Cheson criteria 1999 after a short induction treatment by rituximab and bendamustine
timeFrame: 12 weeks
Secondary outcomes:
measure: Complete response rate according to Cheson criteria 1999 after 24 months of maintenance therapy with Rituximab
timeFrame: 26 months
measure: Partial and objective response rates at the end of induction phase
timeFrame: 12 weeks
measure: Duration of response
timeFrame: From the time of attainment of CR or PR to the date of first documented disease progression, relapse or death from any cause
measure: Progression free survival
timeFrame: From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause.
measure: Overall survival
timeFrame: From the date of randomization to the date of death from any cause
measure: Time before retreatment
timeFrame: From the end of primary treatment until the institution of the next therapy
measure: Immediate toxicity
timeFrame: 12 weeks
measure: Long term toxicity
timeFrame: Until death of the patients
measure: Evaluation of QoL
timeFrame: 7 years
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Arlon
country: Belgium
facility: Clinique Sud du Luxembourg
city: Baudour
country: Belgium
facility: RHMS
city: Bruges
country: Belgium
facility: A. Z. Sint-Jan
city: Bruxelles
country: Belgium
facility: CHU Brugmann
city: Bruxelles
country: Belgium
facility: Université Libre de Bruxelles - Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Université Catholique de Louvain Saint Luc
city: Charleroi
country: Belgium
facility: CH Notre Dame
city: Charleroi
country: Belgium
facility: CHU Charleroi-Vésale
city: Chimay
country: Belgium
facility: Centre de Santé des Fagnes
city: Gosselies
country: Belgium
facility: Clinique Notre Dame de Grace
city: Haine Saint Paul
country: Belgium
facility: Hôpital Jolimont
city: Huy
country: Belgium
facility: CH Hutois
city: Kortrljk
country: Belgium
facility: AZ Groeninge - Campus Maria's Voorzienigheid
city: La Louviere
country: Belgium
facility: CHU Tivoli
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Liège
country: Belgium
facility: CHU de Liège
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Mons
country: Belgium
facility: Clinique Saint Joseph
city: Namur
country: Belgium
facility: Hôpital Sainte Elisabeth
city: Roeselare
country: Belgium
facility: Heilig Hart Ziekenhuis
city: Tournai
country: Belgium
facility: Centre Hospitalier de Wallonie Picarde - CHwapi
city: Verviers
country: Belgium
facility: CH de la Tourelle-Peltzer
city: Yvoir
country: Belgium
facility: UCL Mt Godinne
city: Aix En Provence
country: France
facility: CH du Pays d'Aix
city: Amiens
country: France
facility: CHU Amiens - Hôpital Sud
city: Angers
country: France
facility: CHU d'Angers
city: Antibes
country: France
facility: CH Antibes
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Avignon
country: France
facility: CH d'Avignon - Hôpital Henri Dufaut
city: Bayonne
country: France
facility: Hôpital de Bayonne
city: Beauvais
country: France
facility: Centre Hospitalier de Beauvais
city: Besancon
country: France
facility: CH Jean Minjoz
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne sur mer
country: France
facility: CH Dr Duchenne
city: Bourg en Bresse
country: France
facility: CH de Bourg en Bresse
city: Brest
country: France
facility: CHU Morvan
city: Brive La Gaillarde
country: France
facility: Centre Hospitalier de Brive
city: Béziers
country: France
facility: CH Béziers
city: Caen
country: France
facility: CHU Clémenceau
city: Caen
country: France
facility: Centre Francois Baclesse
city: Cannes
country: France
facility: CH Cannes
city: Chambéry
country: France
facility: CH Chambéry
city: Chartres
country: France
facility: CH de Chartres
city: Châlon sur Saône
country: France
facility: Hôpital de Châlon
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Clamart
country: France
facility: Hôpital d'Instruction des Armées Percy
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Clermont-Ferrand
country: France
facility: Pôle Santé Publique
city: Compiègne
country: France
facility: CH de Compiègne
city: Corbeil Essonne
country: France
facility: Hôpital Sud Francilien
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU le Bocage
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Fréjus
country: France
facility: CH Fréjus St Raphaël
city: Grenoble
country: France
facility: CHU Grenoble
city: Gueret
country: France
facility: Centre Hospitalier de Guéret
city: Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: La Roche sur Yon
country: France
facility: CHD Vendée
city: Laval
country: France
facility: Centre Hospitalier de Laval
city: Le Chesnay
country: France
facility: Hôpital André Mignot
city: Le Mans
country: France
facility: CH Le Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU LIMOGES - Hôpital Universitaire Dupuytren
city: Lorient
country: France
facility: CH de Bretagne Sud
city: Lyon
country: France
facility: Clinique de la Sauvegarde
city: Lyon
country: France
facility: Centre Léon Bérard
city: Macon
country: France
facility: CH les Chanaux
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: CH de Meaux
city: Melun
country: France
facility: Ch Marc Jacquet
city: Metz
country: France
facility: Hôpital Notre Dame de Bon Secours
city: Montpellier
country: France
facility: CH Saint-Eloi
city: Montpellier
country: France
facility: CRCL Val d'Aurelle
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: Mulhouse
country: France
facility: CHU de Mulhouse - Hôpital Emile Muller
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Neuilly
country: France
facility: Hôpital Américain de Paris
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Nimes
country: France
facility: CHU Caremeau
city: Nimes
country: France
facility: Clinique Valdegour
city: Orléans
country: France
facility: CHR de la Source
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Hôtel Dieu
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital St Louis
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Perpignan
country: France
facility: CH Saint Jean
city: Pessac
country: France
facility: Hôpital Haut Levêque
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers - Hôpital de la Milétrie
city: Pontoise
country: France
facility: CH René Dubos
city: Pringy
country: France
facility: Centre Hospitalier de la Région d'Annecy
city: Reims
country: France
facility: Hôpital Robert Debré
city: Reims
country: France
facility: Clinique de Courlancy
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: Clinique Mathilde
city: Saint Cloud
country: France
facility: Centre René Huguenin
city: Saint Malo
country: France
facility: CHU de Saint Malo
city: Saint Priest En Jarest
country: France
facility: CHU Saint-Etienne
city: Saint-quentin
country: France
facility: CH de Saint Quentin
city: St Germain en Laye
country: France
facility: CHG St Germain
city: Toulon
country: France
facility: Hôpital Font Pré
city: Tours
country: France
facility: CHU Bretonneau
city: Troyes
country: France
facility: Hôpital de Troyes
city: Valence
country: France
facility: CH de Valence
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy Brabois
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: CHU Brabois, 54511 Vandoeuvre les Nancy
name: Pierre FEUGIER, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gyan E, Sonet A, Brice P, Anglaret B, Laribi K, Fruchart C, Tilly H, Araujo C, Soubeyran P, Gonzalez H, Morineau N, Nicolas-Virelizier E, Ghesquieres H, Salles B, Bouabdallah R, Orfeuvre H, Fahri J, Couturier O, Xerri L, Feugier P; Lymphoma Study Association (LYSA). Bendamustine and rituximab in elderly patients with low-tumour burden follicular lymphoma. Results of the LYSA phase II BRIEF study. Br J Haematol. 2018 Oct;183(1):76-86. doi: 10.1111/bjh.15513. Epub 2018 Aug 16.