Stage II-IV follicular lymphoma grade 1-3a not previously treated MedDRA version: 20.0 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Rituximab sub cutaneous
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml millig
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion 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 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 =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: • Grade 3b follicular lymphoma • Ann Arbor Stage I • Seropositive for or active viral infection with hepatitis B virus (HBV) defined as: - 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 requirements of treatment • Adult under law-control • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the efficacy of two therapeutic strategies (rituximab SC vs rituximab IV), based on the progression free survival (PFS) assessed according to response criteria for malignant lymphoma 1999 (Cheson 1999), in patients with previously untreated low tumor burden follicular lymphoma.;Secondary Objective: Secondary objectives are to compare rituximab SC versus rituximab IV in terms of : • Overall survival • Response rate at M3 and M12 and best objective response (overall and complete response rates) • Molecular response (BCL2-IGH rearrangement) at M3 and M12 • Time to next anti-lymphoma treatment • Cause of death • Secondary cancers ;Primary end point(s): The primary endpoint is the Progression Free Survival (PFS). The PFS is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. The disease progression status will be assessed using the IWG (Cheson 1999) criteria. If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment.;Timepoint(s) of evaluation of this end point: PFS will be analyzed at the interim analysis (when 51 events occurred) and at the final analysis (when 102 events occurred). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Overall Survival: will be analyzed the final analysis (when 102 events occurred) • Response Rates at M3 (1999 criteria) and M12 (1999 and 2007 criteria): will be analyzed the final analysis (when 102 events occurred) • Best Response Rate according to the response criteria for malignant lymphoma 1999 during the study : will be analyzed the final analysis (when 102 events occurred) • Time to Next Anti-Lymphoma Treatment (TTNLT): will be analyzed the final analysis (when 102 events occurred) • Molecular Response (Bcl-2-IgH rearrangement) at M3 and M12: will be analyzed the final analysis (when 102 events occurred) • Causes of Death : will be analyzed the final analysis (when 102 events occurred) • Secondary cancers : will be analyzed the final analysis (when 102 events occurred) ;Secondary end point(s): • Overall Survival (OS): Overall survival will be measured from the date of randomization to the date of death from any cause. Alive patients will be censored at their last follow-up date. • Response Rates according to the response criteria for malignant lymphoma at M3 (1999) and M12 (1999 and 2014 criteria): Disease response evaluation at M3 and M12 will be used to determine the Response Rate at M3 and M12. 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) 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). • Best Response Rate according to the response criteria for malignant lymphoma 1999 during the study Disease response evaluation at M3, M12 and Follow-Up visits will be used to determine the Best Response Rate. Assessment of response will be based on the International Workshop to S | — |
Countries
France
Contacts
Public ContactStéphanie PICARD
LYSARC
Outcome results
None listed