Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT)

Phase 3

Completed

• Conditions: Follicular Lymphoma
• Interventions: Drug: Rituximab IV; Drug: Rituximab SC

• Registration Number: NCT02303119
• Lead Sponsor: The Lymphoma Academic Research Organisation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-25
• Study First Submitted QC: 2014-11-26
• Study First Posted: 2014-11-27
• Study Start: 2015-02-02
• Primary Completion: 2021-06-29
• Study Completion: 2021-06-29
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-09
• Last Update Posted: 2023-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Rituximab SC	Rituximab IV	1 infusion of intravenous rituximab (375mg/m²) at Day 1, and 7 administrations of sub-cutaneous rituximab (1400mg) at Day 8, Day15, Day 22, Month 3, Month 5, Month 7 and Month 9.
Arm C : Rituximab SC first cycle	Rituximab SC	8 administrations of sub-cutaneous rituximab (1400mg) at Day 8, Day15, Day 22, Month 3, Month 5, Month 7 and Month 9.
Arm B: Rituximab SC	Rituximab SC	1 infusion of intravenous rituximab (375mg/m²) at Day 1, and 7 administrations of sub-cutaneous rituximab (1400mg) at Day 8, Day15, Day 22, Month 3, Month 5, Month 7 and Month 9.
Am A : Rituximab IV	Rituximab IV	4 infusions of intravenous rituximab (375mg/m²) at Day 1, Day 8, Day 15 and D22

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	5.5 years	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

Secondary Outcome Measures

Name	Time	Method
Molecular Response	M3 and M12	Bcl-2-IgH rearrangement
Overall Survival (OS)	5.5 years	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.
Best Response Rate during the study	M3 and M12	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
Time to Next Anti-Lymphoma Treatment (TTNLT)	5.5 years	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.
Response Rates	M3 and M12	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).

Trial Locations

Locations (50)

CH de Pays d'Aix; 🇫🇷 Aix En Provence, France

Hôpital Pasteur; 🇫🇷 Colmar, France

CH d'Avignon - Hôpital Henri Duffaut; 🇫🇷 Avignon, France

CHU Angers; 🇫🇷 Angers, France

Hôpital de Bayonnes; 🇫🇷 Bayonne, France

Institut Bergonié; 🇫🇷 Bordeaux, France

CH de BLOIS; 🇫🇷 Blois, France

Hôpital d'Avicenne; 🇫🇷 Bobigny, France

Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux, France

IHBN - CHU de Caen; 🇫🇷 Caen, France

Clinique du Parc; 🇫🇷 Castelnau Le Lez, France

Chu Estaing; 🇫🇷 Clermont Ferrand, France

CH de Chambéry; 🇫🇷 Chambéry, France

CHU Dijon - Hôpital d'Enfants; 🇫🇷 Dijon, France

Hôpital Henri Mondor; 🇫🇷 Creteil, France

Hôpital Albert Michallon; 🇫🇷 Grenoble, France

Hôpital St Louis; 🇫🇷 La Rochelle, France

CH Départemental Vendée; 🇫🇷 La Roche sur Yon, France

Hôpital André Mignot; 🇫🇷 Le Chesnay, France

Clinique Victor Hugo; 🇫🇷 Le Mans, France

Centre Léon Bérard; 🇫🇷 Lyon, France

CHRU de Lille - Hôpital Claude Hurriez; 🇫🇷 Lille, 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

Hôpital Necker; 🇫🇷 Paris, France

Hôpital Cochin; 🇫🇷 Paris, France

CHR de la Source; 🇫🇷 Orleans, 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 Pontchaillou; 🇫🇷 Rennes, France

Hôpital Robert Debré; 🇫🇷 Reims, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Institut de Cancérologie Lucien Neuwirth; 🇫🇷 Saint Priest en Jarez, France

Hôpital Victor Provo; 🇫🇷 Roubaix, France

Institut de Cancérologie de l'Ouest René Gauducheau; 🇫🇷 Saint Herblain, France

Hôpital Yves Le Foll; 🇫🇷 Saint-Brieuc, France

Hôpital de Hautepierre; 🇫🇷 Strasbourg, France

IUCT Oncopole; 🇫🇷 Toulouse, France

Hôpital Bretonneau; 🇫🇷 Tours, France

CHU Nancy - Hôpital de Brabois; 🇫🇷 Vandoeuvre-les-Nancy, France

CH de TROYES; 🇫🇷 Troyes, France

CH de Valenciennes; 🇫🇷 Valenciennes, France

CH Bretagne Atlantique; 🇫🇷 Vannes, France