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Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT)

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Completed
CT.gov ID
NCT02303119
Collaborator
Roche Pharma AG (Industry)
221
Enrollment
50
Locations
3
Arms
76.8
Actual Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Rituximab IV
  • Drug: Rituximab SC
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
221 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Feb 2, 2015
Actual Primary Completion Date :
Jun 29, 2021
Actual Study Completion Date :
Jun 29, 2021

Arms and Interventions

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

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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).

    3. 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

    4. 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.

    5. Molecular Response [M3 and M12]

      Bcl-2-IgH rearrangement

    Other Outcome Measures

    1. Pharmacokinetic parameters of rituximab will be used to estimate individual area under the concentration curves of rituximab (AUC). [5.5 years]

      The AUC will be used to describe the relationship between rituximab pharmacokinetics and clinical response (objective response, survival).

    2. Causes of death [5.5 years]

      classification by cause of death

    3. Secondary cancers [5.5 years]

      classification by type of cancer

    4. Number of SAE from the first administration [1 year]

      for Rituximab SC as of C1 cohort

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CH de Pays d'Aix Aix En Provence France 13606
    2 CHU Angers Angers France 49933
    3 CH d'Avignon - Hôpital Henri Duffaut Avignon France 84902
    4 Hôpital de Bayonnes Bayonne France 64100
    5 CH de BLOIS Blois France 41016
    6 Hôpital d'Avicenne Bobigny France 93009
    7 Institut Bergonié Bordeaux France 33076
    8 Polyclinique Bordeaux Nord Aquitaine Bordeaux France 33300
    9 IHBN - CHU de Caen Caen France 14033
    10 Clinique du Parc Castelnau Le Lez France 34170
    11 CH de Chambéry Chambéry France 73011
    12 Chu Estaing Clermont Ferrand France 63003
    13 Hôpital Pasteur Colmar France 68024
    14 Hôpital Henri Mondor Creteil France 94010
    15 CHU Dijon - Hôpital d'Enfants Dijon France 21000
    16 Hôpital Albert Michallon Grenoble France 38043
    17 CH Départemental Vendée La Roche sur Yon France 85925
    18 Hôpital St Louis La Rochelle France 17019
    19 Hôpital André Mignot Le Chesnay France 78157
    20 Clinique Victor Hugo Le Mans France 72015
    21 CHRU de Lille - Hôpital Claude Hurriez Lille France 59037
    22 Centre Léon Bérard Lyon France 69373
    23 Hôpital de la Conception Marseille France 13385
    24 Hôpital Mercy Metz France 57085
    25 Hôpital Saint-Eloi Montpellier France 34295
    26 Hôpital Emile Muller Mulhouse France 68070
    27 CHU de Nantes - Hôtel Dieu Nantes France 44093
    28 Institut de Cancérologie du Gard Hématologie clinique Nimes France 30029
    29 CHR de la Source Orleans France 45067
    30 Hôpital Cochin Paris France 75679
    31 Hôpital Necker Paris France 75743
    32 Hôpital Saint Jean Perpignan France 66046
    33 Hôpital Haut Lévêque - Centre François Magendie Pessac France 33604
    34 CHU Lyon Sud Pierre Benite France 69310
    35 CH René Dubos Pontoise France 95300
    36 Centre Hospitalier Annecy-Genevois Pringy France 74374
    37 Hôpital Robert Debré Reims France 51092
    38 Hôpital Pontchaillou Rennes France 35033
    39 Hôpital Victor Provo Roubaix France 59100
    40 Centre Henri Becquerel Rouen France 76038
    41 Institut de Cancérologie de l'Ouest René Gauducheau Saint Herblain France 44805
    42 Institut de Cancérologie Lucien Neuwirth Saint Priest en Jarez France 42271
    43 Hôpital Yves Le Foll Saint-Brieuc France 20000
    44 Hôpital de Hautepierre Strasbourg France 67098
    45 IUCT Oncopole Toulouse France 31059
    46 Hôpital Bretonneau Tours France 37044
    47 CH de TROYES Troyes France 10003
    48 CH de Valenciennes Valenciennes France 59322
    49 CHU Nancy - Hôpital de Brabois Vandoeuvre-les-Nancy France 54500
    50 CH Bretagne Atlantique Vannes France 56017

    Sponsors and Collaborators

    • The Lymphoma Academic Research Organisation
    • Roche Pharma AG

    Investigators

    • Study Chair: Guillaume Cartron, MD PhD, Lymphoma Study Association

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The Lymphoma Academic Research Organisation
    ClinicalTrials.gov Identifier:
    NCT02303119
    Other Study ID Numbers:
    • FLIRT
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by The Lymphoma Academic Research Organisation
    LNH
    CD20+
    follicular
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Rituximab

    Study Results

    No Results Posted as of Sep 1, 2021