- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02303119
Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT) (FLIRT)
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)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
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Aix En Provence, France, 13606
- CH de Pays d'Aix
-
Angers, France, 49933
- Chu Angers
-
Avignon, France, 84902
- CH d'Avignon - Hopital Henri Duffaut
-
Bayonne, France, 64100
- Hôpital de Bayonnes
-
Blois, France, 41016
- CH de Blois
-
Bobigny, France, 93009
- Hôpital d'Avicenne
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Bordeaux, France, 33076
- Institut Bergonié
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Bordeaux, France, 33300
- Polyclinique Bordeaux Nord Aquitaine
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Caen, France, 14033
- IHBN - CHU de Caen
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Castelnau Le Lez, France, 34170
- Clinique du parc
-
Chambéry, France, 73011
- CH de Chambery
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Clermont Ferrand, France, 63003
- CHU Estaing
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Colmar, France, 68024
- Hopital PASTEUR
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Creteil, France, 94010
- Hopital Henri Mondor
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Dijon, France, 21000
- CHU Dijon - Hôpital d'Enfants
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Grenoble, France, 38043
- Hôpital Albert Michallon
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La Roche sur Yon, France, 85925
- CH Départemental Vendée
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La Rochelle, France, 17019
- Hopital St Louis
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Le Chesnay, France, 78157
- Hopital Andre Mignot
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Le Mans, France, 72015
- Clinique Victor Hugo
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Lille, France, 59037
- CHRU de Lille - Hôpital Claude Hurriez
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Lyon, France, 69373
- Centre Léon Bérard
-
Marseille, France, 13385
- Hôpital de la Conception
-
Metz, France, 57085
- Hopital Mercy
-
Montpellier, France, 34295
- Hôpital Saint-Eloi
-
Mulhouse, France, 68070
- Hopital Emile Muller
-
Nantes, France, 44093
- CHU de Nantes - Hotel Dieu
-
Nimes, France, 30029
- Institut de Cancérologie du Gard Hématologie clinique
-
Orleans, France, 45067
- CHR de la Source
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Paris, France, 75679
- Hopital Cochin
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Paris, France, 75743
- Hôpital Necker
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Perpignan, France, 66046
- Hopital Saint Jean
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Pessac, France, 33604
- Hôpital Haut Lévêque - Centre François Magendie
-
Pierre Benite, France, 69310
- CHU Lyon Sud
-
Pontoise, France, 95300
- CH René Dubos
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Pringy, France, 74374
- Centre Hospitalier Annecy-Genevois
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Reims, France, 51092
- Hôpital Robert Debré
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Rennes, France, 35033
- Hôpital Pontchaillou
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Roubaix, France, 59100
- Hôpital Victor Provo
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Rouen, France, 76038
- Centre Henri Becquerel
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Saint Herblain, France, 44805
- Institut de Cancérologie de l'Ouest René Gauducheau
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Saint Priest en Jarez, France, 42271
- Institut de Cancérologie Lucien Neuwirth
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Saint-Brieuc, France, 20000
- Hôpital Yves Le Foll
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Strasbourg, France, 67098
- Hopital de Hautepierre
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Toulouse, France, 31059
- IUCT Oncopole
-
Tours, France, 37044
- Hôpital Bretonneau
-
Troyes, France, 10003
- CH de Troyes
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Valenciennes, France, 59322
- CH de Valenciennes
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Vandoeuvre-les-Nancy, France, 54500
- CHU Nancy - Hôpital de Brabois
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Vannes, France, 56017
- CH Bretagne Atlantique
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Am A : Rituximab IV
4 infusions of intravenous rituximab (375mg/m²) at Day 1, Day 8, Day 15 and D22
|
intra-venous, 375 mg/m²
Other Names:
|
Experimental: Arm B: 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.
|
intra-venous, 375 mg/m²
Other Names:
sub-cutaneous, 1400 mg
Other Names:
|
Experimental: Arm C : Rituximab SC first cycle
8 administrations of sub-cutaneous rituximab (1400mg) at Day 8, Day15, Day 22, Month 3, Month 5, Month 7 and Month 9.
|
sub-cutaneous, 1400 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: 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
|
5.5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 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.
|
5.5 years
|
Response Rates
Time Frame: 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). |
M3 and M12
|
Best Response Rate during the study
Time Frame: 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 |
M3 and M12
|
Time to Next Anti-Lymphoma Treatment (TTNLT)
Time Frame: 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.
|
5.5 years
|
Molecular Response
Time Frame: M3 and M12
|
Bcl-2-IgH rearrangement
|
M3 and M12
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic parameters of rituximab will be used to estimate individual area under the concentration curves of rituximab (AUC).
Time Frame: 5.5 years
|
The AUC will be used to describe the relationship between rituximab pharmacokinetics and clinical response (objective response, survival).
|
5.5 years
|
Causes of death
Time Frame: 5.5 years
|
classification by cause of death
|
5.5 years
|
Secondary cancers
Time Frame: 5.5 years
|
classification by type of cancer
|
5.5 years
|
Number of SAE from the first administration
Time Frame: 1 year
|
for Rituximab SC as of C1 cohort
|
1 year
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Guillaume Cartron, MD PhD, Lymphoma Study Association
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Follicular
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- FLIRT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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