Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT) (FLIRT)

January 9, 2023 updated by: The Lymphoma Academic Research Organisation

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
221

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • 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
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Bordeaux, France, 33300
        • Polyclinique Bordeaux Nord Aquitaine
      • Caen, France, 14033
        • IHBN - CHU de Caen
      • Castelnau Le Lez, France, 34170
        • Clinique du Parc
      • Chambéry, France, 73011
        • Ch De Chambery
      • Clermont Ferrand, France, 63003
        • Chu Estaing
      • Colmar, France, 68024
        • Hôpital Pasteur
      • Creteil, France, 94010
        • Hopital Henri Mondor
      • Dijon, France, 21000
        • CHU Dijon - Hôpital d'Enfants
      • Grenoble, France, 38043
        • Hôpital Albert Michallon
      • La Roche sur Yon, France, 85925
        • CH Départemental Vendée
      • La Rochelle, France, 17019
        • Hopital St Louis
      • Le Chesnay, France, 78157
        • Hôpital André Mignot
      • Le Mans, France, 72015
        • Clinique Victor Hugo
      • Lille, France, 59037
        • CHRU de Lille - Hôpital Claude Hurriez
      • Lyon, France, 69373
        • Centre Leon Berard
      • Marseille, France, 13385
        • Hopital de la Conception
      • Metz, France, 57085
        • Hopital Mercy
      • Montpellier, France, 34295
        • Hopital Saint-Eloi
      • Mulhouse, France, 68070
        • Hôpital Emile Muller
      • Nantes, France, 44093
        • CHU de Nantes - Hôtel Dieu
      • Nimes, France, 30029
        • Institut de Cancérologie du Gard Hématologie clinique
      • Orleans, France, 45067
        • CHR de la Source
      • Paris, France, 75679
        • Hopital Cochin
      • Paris, France, 75743
        • Hôpital Necker
      • Perpignan, France, 66046
        • Hopital Saint Jean
      • Pessac, France, 33604
        • Hôpital Haut Lévêque - Centre François Magendie
      • Pierre Benite, France, 69310
        • CHU Lyon Sud
      • Pontoise, France, 95300
        • CH René Dubos
      • Pringy, France, 74374
        • Centre Hospitalier Annecy-Genevois
      • Reims, France, 51092
        • Hôpital Robert Debré
      • Rennes, France, 35033
        • Hopital Pontchaillou
      • Roubaix, France, 59100
        • Hopital Victor Provo
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Saint Herblain, France, 44805
        • Institut de Cancerologie de L'Ouest Rene Gauducheau
      • Saint Priest en Jarez, France, 42271
        • Institut de Cancérologie Lucien Neuwirth
      • Saint-Brieuc, France, 20000
        • Hôpital Yves Le Foll
      • Strasbourg, France, 67098
        • Hopital de Hautepierre
      • Toulouse, France, 31059
        • IUCT Oncopole
      • Tours, France, 37044
        • Hôpital Bretonneau
      • Troyes, France, 10003
        • CH de Troyes
      • Valenciennes, France, 59322
        • CH de Valenciennes
      • Vandoeuvre-les-Nancy, France, 54500
        • CHU Nancy - Hôpital de Brabois
      • Vannes, France, 56017
        • CH Bretagne Atlantique

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Am A : Rituximab IV
4 infusions of intravenous rituximab (375mg/m²) at Day 1, Day 8, Day 15 and D22
Drug: Rituximab IV
intra-venous, 375 mg/m²
Other Names:
  • MabThera IV
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.
Drug: Rituximab IV
intra-venous, 375 mg/m²
Other Names:
  • MabThera IV
Drug: Rituximab SC
sub-cutaneous, 1400 mg
Other Names:
  • MabThera SC
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.
Drug: Rituximab SC
sub-cutaneous, 1400 mg
Other Names:
  • MabThera SC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Lymphoma Academic Research Organisation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Guillaume Cartron, MD PhD, Lymphoma Study Association

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 2, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 29, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FLIRT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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