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

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ClinicalTrials.gov Identifier: NCT02303119
Recruitment Status : Recruiting
First Posted : November 27, 2014
Last Update Posted : January 4, 2019
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Drug: Rituximab IV Drug: Rituximab SC Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 222 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 : February 2, 2015
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

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 Name: 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 Name: MabThera IV

Drug: Rituximab SC
sub-cutaneous, 1400 mg
Other Name: 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 Name: MabThera SC




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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).


  3. 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


  4. 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. Molecular Response [ Time Frame: 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). [ Time Frame: 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 [ Time Frame: 5.5 years ]
    classification by cause of death

  3. Secondary cancers [ Time Frame: 5.5 years ]
    classification by type of cancer

  4. Number of SAE from the first administration [ Time Frame: 1 year ]
    for Rituximab SC as of C1 cohort



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02303119


Contacts
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Contact: Stephanie Picard +33 (0)4 27 01 27 13 stephanie.picard@lysarc.org

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Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Roche Pharma AG
Investigators
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Study Chair: Guillaume Cartron, MD PhD Lymphoma Study Association

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Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT02303119     History of Changes
Other Study ID Numbers: FLIRT
First Posted: November 27, 2014    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Keywords provided by The Lymphoma Academic Research Organisation:
LNH
CD20+
follicular
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents