BRIEF Bendamustine and Rituximab In Elderly Follicular

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

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

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:

  1. Age >60 ans
  2. Ann Arbor Stage (III-IV vs. I-II)
  3. Hemoglobin level ( < 12g/dL vs. ≥ 12 g/dL)
  4. 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.