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

Study ID
STU 042013-013

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
James Pond
214-648-7030
blake.pond@utsouthwestern.edu

Principal Investigator
Harris Naina

Summary

This randomized phase ii trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage ii, stage iii, or stage iV follicular lymphoma.

Patients are stratified according to FLiPi-1score (1 or 2 vs 3 vs 4 or 5) and GeLF tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms. -

arm a: Patients receive rituximab iV on day 1 and bendamustine hydrochloride iV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab iV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. -

arm B: Patients receive rituximab iV on day 1; bortezomib iV on days 1, 4, 8, and 11 bendamustine hydrochloride iV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab as in arm i. -

arm C: Patients receive rituximab iV on day 1 and bendamustine hydrochloride iV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. immediately after completing induction therapy, patients receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, patients receive rituximab iV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy. Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository. after completion of study therapy, patients are followed up periodically for 15 years.

Participant Eligibility


* 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[Single Quote]Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:
1. Patient must meet >= 1 of the following GELF criteria:
2. Nodal or extranodal mass >= 7 cm
3. At least 3 nodal masses > 3.0 cm in diameter
4. Systemic symptoms due to lymphoma or B symptoms
5. Splenomegaly with spleen > 16 cm by CT scan
6. Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
7. Leukemic presentation (>= 5.0 x 109/L malignant circulating follicular cells)
8. 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):
1. Age >= 60 years
2. Stage III-IV disease
3. At least 1 objective measurable disease parameter
4. Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization
5. Measurable disease in the liver is required if the liver is the only site of lymphoma