Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics
Mantle cell lymphoma (MCL) presents a clinical challenge because it is aggressive and
incurable with chemotherapy. Therefore novel treatment approaches are needed.
MCL has overexpression of NF-kappa B (NF-kappa B), a transcription factor that affects cell
growth and survival, and cyclin D1 that affects cell cycle and growth. These proteins appear
to be involved in the pathogenesis of MCL.
Bortezomib, a proteasome inhibitor that inhibits NF-kappa B and cyclin D1, has demonstrated
activity in patients with relapsed or refractory MCL.
Dose-adjusted-EPOCH-R has excellent activity in MCL, with a complete response (CR) rate of
92%, but patients eventually relapse.
Determine the PFS and OS of DA-EPOCH-RB followed by bortezomib maintenance versus
Diagnosis of mantle cell lymphoma.
No prior treatment except for local radiation or a short course of steroids for control of
Age greater than or equal to 18 years old.
Adequate major organ function unless impairment is due to lymphoma.
To assess the clinical activity and biological effects of bortezomib, patients will
initially receive one cycle of bortezomib alone with sequential tumor biopsies for
All patients will then receive Dose-adjusted (DA)-EPOCH-RB for 6 cycles, and if they have at
least a PR, this will be followed by randomization to either immediate bortezomib
maintenance x 18 months, or to observation, followed by bortezomib if progression occurs.
This study has as a primary goal, to describe progression free survival (PFS) and overall
survival of early bortezomib maintenance versus observation following induction with
bortezomib followed by DA-EPOCH-RB. Important secondary goals are to assess response and
toxicity to bortezomib alone or DA-EPOCH-RB, to evaluate time to progression after receiving
bortezomib following progression on an observation arm, and to assess the biological effects
of bortezomib on untreated MCL.
Allocation: Randomized, Primary Purpose: Treatment
Progression-free survival and overall survival 5 years after completion of study treatment
Wyndham H Wilson, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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