Clinical Trials /

Follicular Lymphoma IV/SC Rituximab Therapy (FLIRT)

NCT02303119

Description:

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.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Follicular Lymphoma IV/SC Rituximab Therapy (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 IDs

  • ORG STUDY ID: FLIRT
  • NCT ID: NCT02303119

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
Rituximab IVMabThera IVAm A : Rituximab IV
Rituximab SCMabThera SCArm B: Rituximab SC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Am A : Rituximab IVActive Comparator4 infusions of intravenous rituximab (375mg/m²) at Day 1, Day 8, Day 15 and D22
  • Rituximab IV
Arm B: Rituximab SCExperimental1 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.
  • Rituximab IV
  • Rituximab SC

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:5.5 years
Safety Issue:
Description: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

Measure:Overall Survival (OS)
Time Frame:5.5 years
Safety Issue:
Description: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.
Measure:Response Rates
Time Frame:M3 and M12
Safety Issue:
Description: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).
Measure:Best Response Rate during the study
Time Frame:M3 and M12
Safety Issue:
Description: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
Measure:Time to Next Anti-Lymphoma Treatment (TTNLT)
Time Frame:5.5 years
Safety Issue:
Description: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.
Measure:Molecular Response
Time Frame:M3 and M12
Safety Issue:
Description:Bcl-2-IgH rearrangement

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Lymphoma Academic Research Organisation

Trial Keywords

  • LNH
  • CD20+
  • follicular

Last Updated