BRIEF Bendamustine and Rituximab In Elderly Follicular

Study Overview
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Brief Summary
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The objective of this study is to evaluate the complete response rate after a short induction treatment with rituximab (375mg/m2)and bendamustine (90mg/m2)in In Elderly (≥ 60 years old) patients with untreated Follicular lymphoma, with an intermediate or high FLIPI score and without high tumor burden. This short induction is followed by a rituximab (375mg/m2)maintenance/ Induction schedule:Rituximab+Bendamustine on Day 1, Bendamustine on Day 2, Rituximab on Day 8, Rituximab on Day 15, rituximab on day 22, Bendamustine on Day 29, Bendamustine on Day 30 Maintenance schedule: 12 infusions of rituximab, each 8 weeks

Official Title
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BRIEF: Bendamustine and Rituximab In Elderly Follicular: A Multicentric Phase II Study Evaluating the Benefit of a Short Induction Treatment by Bendamustine and Rituximab Followed by Maintenance Therapy With Rituximab In Elderly (≥ 60 Years Old) Patients With Untreated Follicular Lymphoma Patients, With an Intermediate or High FLIPI Score

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Rituximab + bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed follicular lymphoma CD20+, all grades except the grade 3b with a lymph node biopsy performed within 6 months before study entry and with material available for central review A minimal initial immunology is required, including : CD20, bcl-2, CD10 and CD5 Age must be ≥ 60 years Patients not previously treated Patients with an intermediate or high risk FLIPI score requiring 2 or more of the following adverse prognostic factors: Age >60 ans Ann Arbor Stage (III-IV vs. I-II) Hemoglobin level ( < 12g/dL vs. ≥ 12 g/dL) Number of nodal areas (< 5 vs. ≥ 5) (Note: LDH should not be considered as an adverse prognostic factor in this study since it is considered as high tumor burden in the GELF criteria) Low burden disease at study entry according to the GELF criteria Patients with at least one measurable site of disease: patients with only blood or marrow or splenic infiltration are excluded Performance status ≤ 2 on the ECOG scale Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) including: Hemoglobin ≥ 8.0 g/dL (5.0 mmol/L) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Adequate renal function: calculated creatinine clearance > 50 ml/min (according to MDRD method) unless these abnormalities are related to lymphoma Adequate hepatic function: Total bilirubin < 2.0 mg/dl (34 µmol/L), AST (SGOT) and ALT (SGPT) ≤ 2.5 x the upper limit of normal unless these abnormalities are related to lymphoma Adequate cardiac function: LEVF ≥ 50% calculated by echocardiography or scintigraphy Having previously signed a written informed consent Exclusion Criteria: Other histological types of lymphoma than follicular lymphoma Grade 3b follicular lymphoma Patients previously on watch and wait since more than 6 months from diagnosis Patients previously treated for lymphoma, except splenectomy Patients with low FLIPI score (0 or 1 adverse prognostic factors not considering elevated LDH) Bulky disease at study entry according to the GELF criteria Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis) Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer or previous cancer in CR without any treatment in the last 5 years Positive HIV, HBV (anti-HBc positivity) and HCV serologies before inclusion Poor Performance status > 2 on the ECOG scale Known contra-indication to study product 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). Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab + bendamustine<br> | Drug: Rituximab + bendamustine<br>* Induction phase: rituximab and bendamustine on Day 1, Bendamustine on Day 2, Rituximab on Day 8, Rituximab on Day 15, Rituximab on Day 22, bendamustine on Day 29, Bendamustine on Day 30<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate according to Cheson criteria 1999 after a short induction treatment by rituximab and bendamustine |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate according to Cheson criteria 1999 after 24 months of maintenance therapy with Rituximab |  | 26 months | 
| Partial and objective response rates at the end of induction phase |  | 12 weeks | 
| Duration of response |  | From the time of attainment of CR or PR to the date of first documented disease progression, relapse or death from any cause | 
| Progression free survival |  | From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause. | 
| Overall survival |  | From the date of randomization to the date of death from any cause | 
| Time before retreatment |  | From the end of primary treatment until the institution of the next therapy | 
| Immediate toxicity |  | 12 weeks | 
| Long term toxicity |  | Until death of the patients | 
| Evaluation of QoL |  | 7 years |