Primary Rituximab and Maintenance

Study Overview
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Brief Summary
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Objectives Primary objective: To evaluate in patients with advanced follicular lymphoma the benefit of maintenance therapy with rituximab after induction of response with chemotherapy plus rituximab in comparison with no maintenance therapy Secondary objective: To evaluate response rates, event driven survival endpoints (EFS, PFS, OS) and quality of life of four different chemotherapy regimens combined with rituximab, with or without maintenance with rituximab, for first line treatment of advanced stage follicular lymphoma. Study Design This is an international open-label, multicentre, randomized study with two treatment phases. In the induction phase patients have to respond to 1st line induction treatment in order to be eligible for randomization to the second phase of maintenance treatment or observation. After the maintenance period patients will be included in the follow up phase for 3 years.

Detailed Description
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Study medication First period: Induction of response with 8 x rituximab combined with 8 cycles of CVP or 6 cycles of CHOP in 21-day cycles or 6 cycles of FCM in 28-day cycles or 6 cycles of MCP in 28-day cycles. Second period: rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment

Official Title
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Advanced Follicular Lymphoma Evaluating the Benefit of Maintenance Therapy With Rituximab (MabThera®) After Induction of Response With Chemotherapy Plus Rituximab in Comparison With no Maintenance Therapy

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed follicular lymphoma grade 1, 2 or 3a. Patients previously untreated. Patients with at least one of the following symptoms requiring initiation of treatment: Bulky disease at study entry according to the GELF criteria: nodal or extranodal mass > 7cm in its greater diameter B symptoms Elevated serum LDH or beta2-microglobulin involvement of at least 3 nodal sites (each with a diameter greater than 3 cm) symptomatic splenic enlargement compressive syndrome pleural/peritoneal effusion Age must be > 18 years. Performance status < 2 on the ECOG scale (see appendix E). Adequate hematological function within 28 days prior to registration (unless those abnormalities are related to lymphoma extension), this includes: Hemoglobin ≥ 8.0 g/dl (5.0 mmol/L) Absolute neutrophil count (ANC) ≥ 1.5 109/L Platelet count ≥ 100 109/L Women are not breast feeding, are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. Men agree not to father a child during participation in the trial and during the 12 months thereafter. Having previously signed a written informed consent form. Exclusion Criteria: Transformation to high-grade lymphoma (secondary to low-grade follicular lymphoma). Grade 3b follicular lymphoma. Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis). Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone. Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer. Major surgery (excluding lymph node biopsy) within 28 days prior to registration. Poor renal function: Serum creatinine > 2.0 mg/dl (197 μmol/L), Poor hepatic function: total bilirubin > 2.0 mg/dl (34 μmol/L), AST (SGOT) > 3 x the upper limit of normal unless these abnormalities are related to lymphoma. Known HIV infection or active HBV or HCV infection. Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease). Judgment is up to the investigator. Life expectancy < 6 months Known sensitivity or allergy to murine products Treatment within a clinical trial within 30 days prior to trial entry Adult patient under tutelage.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A : rituximab maintenance<br>Maintenance with rituximab for 2 years | Drug: Rituximab<br>* rituximab 375 mg/m2 every 8 weeks for 24 months (12 injections) or control with no treatment<br>|
| No Intervention: B : no maintenance<br>No further treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | defined as the time from randomization to progression, relapse, death from any cause. | number of event observed driven : 344 events or 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates, event driven survival endpoints (EFS, PFS, OS) |  | number of event observed driven : 344 events or 10 years | 
| Quality of life |  | number of event observed driven : 344 events or 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lymphoma, follicular, maintenance