FL or non hodgkin lymphoma (NHL) Follicular lymphoma
Conditions
Interventions
All patients will be treated with 6 induction cycles followed by 2 years of
maintenance treatment with rituximab, once every three months.
Sponsors
HOVON
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Relapsed FL grade 1, 2, 3a, see appendix A; • Ann Arbor stage II-IV at relapse, see appendix B; • A biopsy or FNA to show CD20 postivity is required. A biopsy/FNA performed at any time since the most recent therapy is acceptable as long as this shows FL and there is no clinical concern for transformation at the time of study entry. In case clinically transformation is suspected, a biopsy should be obtained at the time of study entry to exclude transformation; • A maximum of five prior systemic treatment regimens (patients who have had a prior allogeneic SCT are excluded; prior autologous SCT (if > 1 year ago) is allowed); • Prior bendamustine is allowed, under the following conditions: * Only one prior treatment (with a maximum of 6 cycles) with bendamustine is allowed * Patients must have had a PR or CR following prior use of bendamustine * Prior treatment with bendamustine must have taken place >=24 months ago (measured from the start of prior bendamustine treatment, i.e. approximately 18 months from the end of prior bendamustine treatment) • 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 criteria: 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 = 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 (unless bone marrow infiltration), platelet count >= 100x 109/l (unless bone marrow infiltration), creatinine clearance >= 50 ml/min, total bilirubin
Exclusion criteria
Exclusion criteria: • Rituximab-refractory patients (definition: progression during or within 6 months after rituximab containing immunochemotherapy. Patients relapsing under rituximab maintenance treatment are eligible, if at biopsy or FNA CD20 positivity is confirmed); • Clinical or histologic signs of transformation. Patients with a prior transformed phase of FL are eligible IF there are currently no signs of transformation and there is histologic proof that the current phase is not transformed AND the transformed phase occurred >2 years ago; • Prior allogeneic SCT; • Prior autologous SCT less than one year ago; • Any prior use of an immunomodulatory agents such as lenalidomide, pomalidomide or CC-122; • Concurrent use of other anti-cancer agents or treatments; • The use of prednisolone for any other indication than lymphoma treatment is allowed at a maximum dose of or equivalent to 20 mg prednisolone; • Concurrent use of allopurinol, e.g. because of gout. Patients with gout are advised to switch to another anti-gout medication, because of the risk of Stevens-Johnson Syndrome observed in patients using bendamustine and allopurinol; • Use of any other experimental drug or therapy within 28 days of baseline; • Hepatitis B (including HBcAb) 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; • Recent vaccination for yellow fever (within 4 weeks before registration) • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: • dose limiting toxicity • recommended dose level of lenalidomide and of bendamustine in combination with rituximab (for arm B of the phase II of the study) Phase II: • complete remission rate • rate of severe toxicity. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Overall response rate following induction treatment and at the end of maintenance rituximab • Molecular response rate. • Event free survival (EFS; i.e. time from registration to induction failure, progression, relapse or death, whichever occurs first). A patient counts as induction failure if no PR or CR was achieved after induciton. • progression free survival (PFS; i.e. time from registration to disease progression, relapse or death, whichever occurs first); • disease free survival (DFS; i.e. time from CR to relapse or death, whichever comes first) • time to next antilymphoma treatment • overall survival (O.S.; i.e. time from registration until death) • relative dose intensity of lenalidomide and, if applicable, bendamustine | — |
Countries
Netherlands
Outcome results
None listed