Clinical trial NCT02303119: Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT)
Official title: A Randomized Phase III Trial Evaluating Two Strategies of Rituximab Administration for the Treatment of First Line/Low Tumor Burden Follicular Lymphoma (Follicular Lymphoma IV/SC Rituximab Therapy)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Follicular Lymphoma
Keywords: LNH
CD20+
follicular
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2014-11-27
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patient will receive either one infusion of rituximab IV and seven administrations of rituximab SC (experimental arm) or four infusions of rituximab IV (standard arm).

The hypothesis is that the use of rituximab by sub cutaneous route and the scheme of administration could:

* optimize rituximab exposure leading to improve response rate
* increase adaptative response and then improve long-term control disease.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed follicular lymphoma CD20+ grade 1, 2 and 3a by biopsy within 4 months before signing informed consent
* Have a bone marrow biopsy within 4 months before the first study drug administration
* Have no prior therapy except surgery for diagnosis
* Aged 18 years or more with no upper age limit
* ECOG performance status 0-2
* Ann Arbor Stage II, III or IV
* Bi-dimensionally measurable disease defined by at least one single node or tumor lesion \> 1.5 cm assessed by CT scan and/or clinical examination
* With low-tumor burden defined as:

  * Nodal or extra-nodal tumor mass with diameter less than 7 cm in its greater diameter
  * And involvement of less than 3 nodal or extra nodal sites with diameter greater than 3 cm
  * And absence of B symptoms
  * And no symptomatic splenomegaly
  * And no compression syndrome (ureteral, orbital, gastrointestinal...)
  * And no pleural or peritoneal serous effusion
  * And no cytopenia, with hemoglobin \> 10 g/dL (6.25mmol/L) and absolute neutrophil count\> 1.5 G/L and platelets \> 100 G/L within 28 days before the randomization
  * And LDH \< ULN within 28 days before the randomization
  * And β2 microglobulin \< ULN within 28 days before the randomization
* Have signed an informed consent
* Must be covered by a social security system

Exclusion Criteria:

* Grade 3b follicular lymphoma
* Ann Arbor Stage I
* Seropositive for or active viral infection with hepatitis B virus (HBV) HBs Ag positive HBs Ag negative, anti-HBs antibody positive and/or anti-HBc antibody positive and detectable viral DNA

Note:

Patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative are eligible Patients who are seropositive due to a history of hepatitis B vaccine are eligible

* Known seropositive for, or active viral infection with hepatitis C virus (HCV)
* Known seropositive for, or active viral infection with Human Immunodeficiency Virus (HIV)
* Any of the following laboratory abnormalities within 28 days before the randomization:

Total bilirubin or GGT or AST or ALT \> 3 ULN. Calculated creatinine clearance (Cockcroft and Gault formula) \< 60 mL /min

* Presence or history of CNS involvement by lymphoma
* Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
* Patient with mental deficiency preventing proper understanding of the informed consent and the requirements of treatment.
* Adult under law-control
* Adult under tutelage
* Contraindication to use rituximab or known sensitivity or allergy to murine products
* Pregnant or lactating females.
* Concomitant disease requiring prolonged use of corticosteroids or corticosteroids administration for lymphoma within 28 days before the first study drug administration.
* Male and female patients of childbearing potential who cannot or do not wish to use an effective method of contraception, during the study treatment and for 12 months thereafter.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 5.5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5.5 years
measure: Response Rates
timeFrame: M3 and M12
measure: Best Response Rate during the study
timeFrame: M3 and M12
measure: Time to Next Anti-Lymphoma Treatment (TTNLT)
timeFrame: 5.5 years
measure: Molecular Response
timeFrame: M3 and M12
Other outcomes:
measure: Pharmacokinetic parameters of rituximab will be used to estimate individual area under the concentration curves of rituximab (AUC).
timeFrame: 5.5 years
measure: Causes of death
timeFrame: 5.5 years
measure: Secondary cancers
timeFrame: 5.5 years
measure: Number of SAE from the first administration
timeFrame: 1 year
Locations:
city: Aix En Provence
country: France
facility: CH de Pays d'Aix
city: Angers
country: France
facility: CHU Angers
city: Avignon
country: France
facility: CH d'Avignon - Hôpital Henri Duffaut
city: Bayonne
country: France
facility: Hôpital de Bayonnes
city: Blois
country: France
facility: CH de BLOIS
city: Bobigny
country: France
facility: Hôpital d'Avicenne
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Caen
country: France
facility: IHBN - CHU de Caen
city: Castelnau Le Lez
country: France
facility: Clinique du Parc
city: Chambéry
country: France
facility: CH de Chambéry
city: Clermont Ferrand
country: France
facility: Chu Estaing
city: Colmar
country: France
facility: Hôpital Pasteur
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hôpital d'Enfants
city: Grenoble
country: France
facility: Hôpital Albert Michallon
city: La Roche sur Yon
country: France
facility: CH Départemental Vendée
city: La Rochelle
country: France
facility: Hôpital St Louis
city: Le Chesnay
country: France
facility: Hôpital André Mignot
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Hurriez
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la Conception
city: Metz
country: France
facility: Hôpital Mercy
city: Montpellier
country: France
facility: Hôpital Saint-Eloi
city: Mulhouse
country: France
facility: Hôpital Emile Muller
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nimes
country: France
facility: Institut de Cancérologie du Gard Hématologie clinique
city: Orleans
country: France
facility: CHR de la Source
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker
city: Perpignan
country: France
facility: Hôpital Saint Jean
city: Pessac
country: France
facility: Hôpital Haut Lévêque - Centre François Magendie
city: Pierre Benite
country: France
facility: CHU Lyon Sud
city: Pontoise
country: France
facility: CH René Dubos
city: Pringy
country: France
facility: Centre Hospitalier Annecy-Genevois
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Roubaix
country: France
facility: Hôpital Victor Provo
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest René Gauducheau
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Saint-Brieuc
country: France
facility: Hôpital Yves Le Foll
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: IUCT Oncopole
city: Tours
country: France
facility: Hôpital Bretonneau
city: Troyes
country: France
facility: CH de TROYES
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy - Hôpital de Brabois
city: Vannes
country: France
facility: CH Bretagne Atlantique
Study officials:
affiliation: Lymphoma Study Association
name: Guillaume Cartron, MD PhD
role: STUDY_CHAIR
References: