Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT)

Follicular Lymphoma Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02303119
• Other study ID #: FLIRT
• Status: Completed
• Phase: Phase 3
• Start date: February 2, 2015
• Est. completion date: June 29, 2021

Study information

• Verified date: January 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: June 29, 2021
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß2 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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Rituximab IV
intra-venous, 375 mg/m²
• Rituximab SC
sub-cutaneous, 1400 mg

Locations

Country	Name	City	State
France	CH de Pays d'Aix	Aix En Provence
France	CHU Angers	Angers
France	CH d'Avignon - Hôpital Henri Duffaut	Avignon
France	Hôpital de Bayonnes	Bayonne
France	CH de BLOIS	Blois
France	Hôpital d'Avicenne	Bobigny
France	Institut Bergonié	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	IHBN - CHU de Caen	Caen
France	Clinique du Parc	Castelnau Le Lez
France	CH de Chambéry	Chambéry
France	Chu Estaing	Clermont Ferrand
France	Hôpital Pasteur	Colmar
France	Hôpital Henri Mondor	Creteil
France	CHU Dijon - Hôpital d'Enfants	Dijon
France	Hôpital Albert Michallon	Grenoble
France	CH Départemental Vendée	La Roche sur Yon
France	Hôpital St Louis	La Rochelle
France	Hôpital André Mignot	Le Chesnay
France	Clinique Victor Hugo	Le Mans
France	CHRU de Lille - Hôpital Claude Hurriez	Lille
France	Centre Léon Bérard	Lyon
France	Hôpital de la Conception	Marseille
France	Hôpital Mercy	Metz
France	Hôpital Saint-Eloi	Montpellier
France	Hôpital Emile Muller	Mulhouse
France	CHU de Nantes - Hôtel Dieu	Nantes
France	Institut de Cancérologie du Gard Hématologie clinique	Nimes
France	CHR de la Source	Orleans
France	Hôpital Cochin	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint Jean	Perpignan
France	Hôpital Haut Lévêque - Centre François Magendie	Pessac
France	CHU Lyon Sud	Pierre Benite
France	CH René Dubos	Pontoise
France	Centre Hospitalier Annecy-Genevois	Pringy
France	Hôpital Robert Debré	Reims
France	Hôpital Pontchaillou	Rennes
France	Hôpital Victor Provo	Roubaix
France	Centre Henri Becquerel	Rouen
France	Institut de Cancérologie de l'Ouest René Gauducheau	Saint Herblain
France	Institut de Cancérologie Lucien Neuwirth	Saint Priest en Jarez
France	Hôpital Yves Le Foll	Saint-Brieuc
France	Hôpital de Hautepierre	Strasbourg
France	IUCT Oncopole	Toulouse
France	Hôpital Bretonneau	Tours
France	CH de TROYES	Troyes
France	CH de Valenciennes	Valenciennes
France	CHU Nancy - Hôpital de Brabois	Vandoeuvre-les-Nancy
France	CH Bretagne Atlantique	Vannes

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Roche Pharma AG

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic parameters of rituximab will be used to estimate individual area under the concentration curves of rituximab (AUC).	The AUC will be used to describe the relationship between rituximab pharmacokinetics and clinical response (objective response, survival).	5.5 years
Other	Causes of death	classification by cause of death	5.5 years
Other	Secondary cancers	classification by type of cancer	5.5 years
Other	Number of SAE from the first administration	for Rituximab SC as of C1 cohort	1 year
Primary	Progression Free Survival (PFS)	Time from randomization into the study to the first observation of documented disease progression or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment	5.5 years
Secondary	Overall Survival (OS)	time from the date of randomization to the date of death from any cause. Alive patients will be censored at their last follow-up date.	5.5 years
Secondary	Response Rates	Disease response evaluation, assessment will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma) according to Cheson 1999 (M3 and M12) and according to Cheson 2014 (M12 only).; The response rates will be described for each modality (CR, CRu, PR, SD and PD) and the Overall response rates (CR+CRu+PR) will also be described at the two time points (M3 & M12).	M3 and M12
Secondary	Best Response Rate during the study	Best disease response, assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999)).; The response rates will be described for each modality (CR, CRu, PR, SD and PD) and the Overall response rates (CR+CRu+PR) will also be described	M3 and M12
Secondary	Time to Next Anti-Lymphoma Treatment (TTNLT)	time from randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio-immunotherapy, immunotherapy…). Patients continuing in response or who are lost to follow-up will be censored on their last visit date. Patients who died (due to any cause) before having received a new anti-lymphoma treatment will be included in the statistical analysis with death being counted as an event.	5.5 years
Secondary	Molecular Response	Bcl-2-IgH rearrangement	M3 and M12