Research Study Summary
ECOG E2408 A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to try and improve the outcomes for patients with untreated high risk follicular lymphoma. We will evaluate two new treatment approaches for the treatment of follicular lymphoma. These new treatment agents will be added to standard Bendamustine-Rituximab (BR) induction therapy and to standard rituximab continuation therapy as discussed below. The purpose of making these additions to standard therapy is to see if induction therapy and/or continuation therapy can improve your outcome (i.e., longer remission and possibly improved survival). We also want to make sure that any side effects from these treatments are tolerable.
There are three different treatment groups. A computer will randomly choose which treatment group you will be treated with. All treatment groups will receive one initial "induction" with rituximab and chemotherapy for 6 treatment cycles, which will be followed by a "continuation" treatment that will last for two years (see Study Chart on page 6).
Group 1 consists of standard BR induction (Arm A) and standard rituximab continuation (Arm D). Induction therapy consists of a standard combination of drugs called BR (bendamustine and rituximab combined) to get your disease into remission. You will receive 6 cycles of BR induction. These cycles are given every 4 weeks. Continued rituximab treatments after induction therapy have been shown in some studies to prolong the length of remission and also improve survival.
Therefore, after BR induction, you will receive one dose of rituximab alone every 8 weeks for a total of 2 years (called: continuation).
If you are assigned to group 2, you will receive BVR induction (Arm B) and standard rituximab continuation (Arm E). You will receive a drug called Bortezomib that targets the genes inside cancer cells added to BR (called: BVR). You will receive 6 cycles of BVR induction treatment. These cycles are given every 4 weeks. In this study we are evaluating if BVR is better able to stop the growth of lymphoma than just BR. We also want to find out if the side effects of this treatment are tolerable. After BVR induction, you will continue with rituximab treatment alone (called: continuation) given as one dose every 8 weeks for a total of 2 years.
If you are assigned to group 3, you will receive standard BR induction (Arm C) for a total of 6 cycles. These cycles are given every 4 weeks. After induction therapy, you will continue with treatment called continuation (Arm F). Continuation treatment will consist of rituximab combined with the new drug called lenalidomide that targets the genes inside cancer cells. Rituximab will be given once every 8 weeks for a total of 2 years, while lenalidomide will be given every month for 1 year (i.e., during the first year of rituximab). Lenalidomide is a drug that has been reported to be effective in relapsed lymphoma. In this study we are evaluating if lenalidomide combined with rituximab is better able to stop the growth of lymphoma than just rituximab alone. We also want to find out if the side effects of this treatment are tolerable.
The drugs bortezomib and lenalidomide are investigational for this specific study diagnosis (i.e., they have not been approved by the FDA for the treatment of follicular lymphoma). Bortezomib is FDA approved to treat newly diagnosed and relapsed or refractory multiple myeloma (a type of blood and bone marrow cancer) and it is also FDA approved to treat relapsed mantle-cell lymphoma. Lenalidomide is FDA approved for the treatment of some patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes.
Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy.
Patient Inclusion Criteria:
- Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology
- Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., = 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology
- Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy) required if the interval since tissue diagnosis of low-grade malignant lymphoma is > 24 months
- Bone marrow biopsy alone not acceptable
- Stage II, III, or IV AND grade 1, 2, or 3a disease
- Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D’Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:
- Patient must meet ≥ 1 of the following GELF criteria:
- Nodal or extranodal mass ≥ 7 cm
- At least 3 nodal masses > 3.0 cm in diameter
- Systemic symptoms due to lymphoma or B symptoms
- Splenomegaly with spleen > 16 cm by CT scan
- Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
- Leukemic presentation (≥ 5.0 x 109/L malignant circulating follicular cells)
- Cytopenias (polymorphonuclear leukocytes < 1.0 X 109/L, hemoglobin < 10 g/dL, and/or platelets < 100 x 109/L)
- Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):
- Age ≥ 60 years
- Stage III-IV disease
- At least 1 objective measurable disease parameter
- Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization
- Measurable disease in the liver is required if the liver is the only site of lymphoma
Patient Exclusion Criteria:
- No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma
- Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy
- A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed
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