Relapsed CD20+ 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.
In the induction cycles in the phase I part of the study, le
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
P.O. box 5201
3008 AE Rotterdam
Tel: +31 10 7041560
Fax: +31 10 7041028
e-mail: hdc@erasmusmc.nl
Eligibility
Inclusion criteria
Inclusion criteria: 1. Relapsed FL grade 1, 2, 3a; 2. Ann Arbor stage II-IV at relapse; 3. The lymphoma at relapse must be CD20+. To establish this, and to exclude transformation to aggressive lymphoma, a biopsy at relapse is strongly recommended; 4. 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); 5. Subjects must have an indication for treatment based on one or more of the following criteria: A. Involvement of at least 3 nodal sites, each with a diameter > 3 cm; B. Symptomatic splenomegaly; C. Bulky disease at study entry according to the GELF criteria: nodal or extranodal mass (except spleen) > 7 cm in its greatest diameter; D. 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); E. Hb < 10 g/dl (6.2 mmol/l) (if caused by bone marrow infiltration and not otherwise explained); F. Thrombocytopenia: platelets < 100x109/l caused by bone marrow infiltration; G. Organ compression syndrome (e.g. hydronephrosis caused by lymphadenopathy); H. Pleural/peritoneal effusion; I. Symptomatic extranodal manifestations. 6. Measurable disease as defined in appendix C (patients with only bone marrow involvement are therefore not eligible); 7. Age ≥ 18 years; 8. Able to adhere to the study visit schedule and other protocol requirements; 9. WHO performance status of 0-2; 10. 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; 11. 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; 12. 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; 13. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Rituximab-refractory patients (definition: progression during or within 6 months after rituximab containing immunochemotherapy or rituximab maintenance treatment); 2. Clinical or histologic signs of transformation; 3. Prior allogeneic SCT; 4. Prior autologous SCT less than one year ago; 5. Any prior use of lenalidomide or bendamustine; 6. Concurrent use of other anti-cancer agents or treatments; 7. Use of any other experimental drug or therapy within 28 days of baseline; 8. Hepatitis B sAg positive, Hepatitis C positive and/or HIV positive patients; 9. Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP); 10. Active fungal, bacterial, and/or viral infection; 11. Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide); 12. Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs; 13. Intolerance of exogenous protein administration, or known allergy to murine products; 14. Uncontrolled hyperthyroidism or hypothyroidism; 15. Neuropathy ≥ grade 2 at time of inclusion; 16. Clinically symptomatic severe cardiac dysfunction (NYHA III-IV); 17. Clinically symptomatic severe pulmonary dysfunction; 18. Severe neurologic or psychiatric diseases.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For the phase I part of the study: To determine the dose limiting toxicity (DLT) and recommended dose level (RDL) of lenalidomide and bendamustine given in combination with rituximab for the phase II part of the study. For the phase II of the study: To determine the efficacy and toxicity of the two arms of the study (arm A: lenalidomide and rituximab, and arm B: lenalidomide, rituximab and bendamustine) in patients with relapsed follicular lymphoma (FL) and to identify the most promising of these two treatment arms. | — |
Secondary
| Measure | Time frame |
|---|---|
| In the phase II part of the study: 1. To determine the value of PET-CT scanning in response assessment of FL patients; 2. To identify predictive factors for response. For this purpose various tissue–associated markers will be explored both on tumor cells and on non-malignant cells of the tumor microenvironment using tissue microarrays or primary lymphoma biopsy samples. These studies will be supported by gene expression profiling in a selection of the patients. Results will be correlated to clinical outcome as well as PET-CT results and circulating subsets of T cells and NK cells; 3. To specifically explore treatment-induced alterations in non-malignant immune cell populations. For this purpose, alterations during treatment in these populations in the peripheral blood and at the tissue level of involved lymh nodes will be performed. For the latter analysis sequential fine needle aspirations and biopsies will be performed in a selection of patients. The sequential biopsies will also be used to study the biological mechanisms of tumor cell kill. | — |
Contacts
Public ContactM.J. Kersten
Meibergdreef 9, F4-224
Outcome results
None listed