Originele protocol


Efficacy and toxicity of lenalidomide and rituximab with or without bendamustine in patients ≥ 18 years with relapsed follicular lymphoma


Inclusion criteria

  • Relapsed FL grade 1, 2, 3a;
  • Ann Arbor stage II-IV at relapse;
  • The lymphoma at relapse must be CD20+. To establish this, and to exclude transformation to aggressive lymphoma, a biopsy at relapse is strongly recommended;
  • A maximum of three prior treatment regimens (patients that have had a prior allogeneic SCT are excluded; prior autologous SCT (if > 1 year ago) is allowed);
  • Subjects must have an indication for treatment based on one or more of the following criteria:
    • Involvement of at least 3 nodal sites, each with a diameter > 3 cm
    • Symptomatic splenomegaly
    • Bulky disease at study entry according to the GELF criteria62: nodal or extranodal mass (except spleen) > 7 cm in its greatest diameter
    • B-symptoms (absence or presence of fever and/or night sweats and/or unexplained loss of 10% of body weight or more in the 6 months preceding diagnosis)
    • Hb < 10 g/dl (6.2 mmol/l) (if caused by bone marrow infiltration and not otherwise explained)
    • Thrombocytopenia: platelets < 100×109/l caused by bone marrow infiltration
    • Organ compression syndrome (e.g. hydronephrosis caused by lymphadenopathy)
    • Pleural/peritoneal effusion
    • Symptomatic extranodal manifestations;
  • Measurable disease as defined in appendix C (patients with only bone marrow involvement are therefore not eligible);
  • Age ≥ 18 years;
  • Able to adhere to the study visit schedule and other protocol requirements;
  • WHO performance status of 0-2;
  • Laboratory test results within these ranges: absolute neutrophil count ≥ 1.5x 109/l, platelet count ≥ 100x 109/l, creatinin clearance ≥ 50 ml/min, total bilirubin ≤ 30 µmol/l (1,75 mg/dl), AST & ALT ≤ 3x ULN;
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 10 – 14 days prior to and again within 24 hours of starting lenalidomide treatment;
  • Patients must be willing and capable to use adequate contraception during the therapy (all men, all pre-menopausal women). Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan;
  • Written informed consent.

Exclusion criteria

  • Rituximab-refractory patients (definition: progression during or within 6 months after rituximab containing immunochemotherapy or rituximab maintenance treatment);
  • Clinical or histologic signs of transformation;
  • Prior allogeneic SCT;
  • Prior autologous SCT less than one year ago;
  • Any prior use of lenalidomide or bendamustine;
  • Concurrent use of other anti-cancer agents or treatments;
  • Use of any other experimental drug or therapy within 28 days of baseline;
  • Hepatitis B sAg positive, Hepatitis C positive and/or HIV positive patients;
  • Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP);
  • Active fungal, bacterial, and/or viral infection;
  • Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide);
  • Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs;
  • Intolerance of exogenous protein administration, or known allergy to murine products;
  • Uncontrolled hyperthyroidism or hypothyroidism;
  • Neuropathy ≥ grade 2 at time of inclusion;
  • Clinically symptomatic severe cardiac dysfunction (NYHA III-IV, see appendix G);
  • Clinically symptomatic severe pulmonary dysfunction;
  • Severe neurologic or psychiatric diseases;
  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection);
  • History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer (TNM stage of T1a or T1b);
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule