BRIEF Bendamustine and Rituximab In Elderly Follicular

Follicular Lymphoma Clinical Trial

— BRIEF  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01313611
• Other study ID #: BRIEF
• Status: Terminated
• Phase: Phase 2
• First received: February 21, 2011
• Last updated: March 6, 2018
• Start date: February 2011
• Est. completion date: December 2017

Study information

• Verified date: March 2018
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: December 2017
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Rituximab + bendamustine
Induction phase: rituximab and 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

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	Clinique Sud du Luxembourg	Arlon
Belgium	RHMS	Baudour
Belgium	A. Z. Sint-Jan	Bruges
Belgium	CHU Brugmann	Bruxelles
Belgium	Université Catholique de Louvain Saint Luc	Bruxelles
Belgium	Université Libre de Bruxelles - Hôpital Erasme	Bruxelles
Belgium	CH Notre Dame	Charleroi
Belgium	CHU Charleroi-Vésale	Charleroi
Belgium	Centre de Santé des Fagnes	Chimay
Belgium	Clinique Notre Dame de Grace	Gosselies
Belgium	Hôpital Jolimont	Haine Saint Paul
Belgium	CH Hutois	Huy
Belgium	AZ Groeninge - Campus Maria's Voorzienigheid	Kortrljk
Belgium	CHU Tivoli	La Louviere
Belgium	CHR de la Citadelle	Liège
Belgium	CHU de Liège	Liège
Belgium	CHU Ambroise Paré	Mons
Belgium	Clinique Saint Joseph	Mons
Belgium	Hôpital Sainte Elisabeth	Namur
Belgium	Heilig Hart Ziekenhuis	Roeselare
Belgium	Centre Hospitalier de Wallonie Picarde - CHwapi	Tournai
Belgium	CH de la Tourelle-Peltzer	Verviers
Belgium	UCL Mt Godinne	Yvoir
France	CH du Pays d'Aix	Aix En Provence
France	CHU Amiens - Hôpital Sud	Amiens
France	CHU d'Angers	Angers
France	CH Antibes	Antibes
France	CH Victor Dupouy	Argenteuil
France	CH d'Avignon - Hôpital Henri Dufaut	Avignon
France	Hôpital de Bayonne	Bayonne
France	Centre Hospitalier de Beauvais	Beauvais
France	CH Jean Minjoz	Besancon
France	CH Béziers	Béziers
France	Centre Hospitalier de Blois	Blois
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	CH Dr Duchenne	Boulogne sur mer
France	CH de Bourg en Bresse	Bourg en Bresse
France	CHU Morvan	Brest
France	Centre Hospitalier de Brive	Brive La Gaillarde
France	Centre Francois Baclesse	Caen
France	CHU Clémenceau	Caen
France	CH Cannes	Cannes
France	Hôpital de Châlon	Châlon sur Saône
France	CH Chambéry	Chambéry
France	CH de Chartres	Chartres
France	Hôpital Antoine Béclère	Clamart
France	Hôpital d'Instruction des Armées Percy	Clamart
France	CHU Estaing	Clermont-Ferrand
France	Pôle Santé Publique	Clermont-Ferrand
France	CH de Compiègne	Compiègne
France	Hôpital Sud Francilien	Corbeil Essonne
France	Hôpital Henri Mondor	Créteil
France	CHU le Bocage	Dijon
France	CH de Dunkerque	Dunkerque
France	CH Fréjus St Raphaël	Fréjus
France	CHU Grenoble	Grenoble
France	Centre Hospitalier de Guéret	Gueret
France	Hôpital Bicêtre	Kremlin Bicêtre
France	CHD Vendée	La Roche sur Yon
France	Centre Hospitalier de Laval	Laval
France	Hôpital André Mignot	Le Chesnay
France	CH Le Mans	Le Mans
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans
France	CHRU de Lille - Hôpital Claude Huriez	Lille
France	CHU LIMOGES - Hôpital Universitaire Dupuytren	Limoges
France	CH de Bretagne Sud	Lorient
France	Centre Léon Bérard	Lyon
France	Clinique de la Sauvegarde	Lyon
France	CH les Chanaux	Macon
France	Institut Paoli Calmettes	Marseille
France	CH de Meaux	Meaux
France	Ch Marc Jacquet	Melun
France	Hôpital Notre Dame de Bon Secours	Metz
France	CH Saint-Eloi	Montpellier
France	CRCL Val d'Aurelle	Montpellier
France	Centre Azuréen de Cancérologie	Mougins
France	CHU de Mulhouse - Hôpital Emile Muller	Mulhouse
France	Centre Catherine de Sienne	Nantes
France	CHU Hôtel Dieu	Nantes
France	Hôpital Américain de Paris	Neuilly
France	Centre Antoine Lacassagne	Nice
France	CHU de Nice	Nice
France	CHU Caremeau	Nimes
France	Clinique Valdegour	Nimes
France	CHR de la Source	Orléans
France	Hôpital de la Pitié Salpétrière	Paris
France	Hôpital Hôtel Dieu	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital St Louis	Paris
France	Institut Curie	Paris
France	CH Saint Jean	Perpignan
France	Hôpital Haut Levêque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	CHU de Poitiers - Hôpital de la Milétrie	Poitiers
France	CH René Dubos	Pontoise
France	Centre Hospitalier de la Région d'Annecy	Pringy
France	Clinique de Courlancy	Reims
France	Hôpital Robert Debré	Reims
France	Hôpital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	Clinique Mathilde	Rouen
France	Centre René Huguenin	Saint Cloud
France	CHU de Saint Malo	Saint Malo
France	CHU Saint-Etienne	Saint Priest En Jarest
France	CH de Saint Quentin	Saint-quentin
France	CHG St Germain	St Germain en Laye
France	Hôpital Font Pré	Toulon
France	CHU Bretonneau	Tours
France	Hôpital de Troyes	Troyes
France	CH de Valence	Valence
France	CHU Nancy Brabois	Vandoeuvre les Nancy
France	Centre Hospitalier Bretagne Atlantique	Vannes
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate according to Cheson criteria 1999 after a short induction treatment by rituximab and bendamustine		12 weeks
Secondary	Complete response rate according to Cheson criteria 1999 after 24 months of maintenance therapy with Rituximab		26 months
Secondary	Partial and objective response rates at the end of induction phase		12 weeks
Secondary	Duration of response		From the time of attainment of CR or PR to the date of first documented disease progression, relapse or death from any cause
Secondary	Progression free survival		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.
Secondary	Overall survival		From the date of randomization to the date of death from any cause
Secondary	Time before retreatment		From the end of primary treatment until the institution of the next therapy
Secondary	Immediate toxicity		12 weeks
Secondary	Long term toxicity		Until death of the patients
Secondary	Evaluation of QoL		7 years