EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma

This study will evaluate the effectiveness of etoposide, prednisone, vincristine,
cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating
mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of
the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug
called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92
percent had a complete remission of their disease after treatment with EPOCH-R. This study
will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished
will lengthen the time before the disease relapses and improve the overall cure rate.

Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study.
Candidates are screened with a medical history and physical examination, blood and urine
tests, electrocardiogram, multi-gated acquisition scan (MUGA) or echocardiogram, imaging
studies and biopsy to determine the extent of disease, and possible colonoscopy.

Participants undergo treatment in three parts, as follows:

- Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug
is injected into a vein over about 30 seconds.

- Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4
weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week
cycles, with all drugs administered over the first 5 days of each cycle. Patients take
prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a
96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered
through a lightweight, portable infusion pump. Rituximab is given by vein over several
hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given
by vein over 30 seconds on day 1 before the rituximab and again on day 4.
Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the
chemotherapy infusion is completed. Patients are taught how to self inject granulocyte
colony stimulating factor (G-CSF), a drug that helps boost white cell counts after
chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of
each cycle beginning day 6. Patients also take an antibiotic to help prevent infection
during chemotherapy.

- Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly
assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses
over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue
for up to 18 months or until the disease comes back or worsens. Patients who are
assigned to the group that does not receive bortezomib will be offered the drug if their
disease relapses.

During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or
other fluids to look at different genes and proteins that may be involved in the development
of their lymphoma or the reaction of the immune system. A tissue biopsy is done before
treatment begins and a day after treatment starts. Disease progress is followed with computed
tomography (CT) scans and blood tests. When treatment is completed, patients whose cancer has
disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease
remains or recurs may be offered participation in another protocol if an appropriate one is
available or are returned to the care of their local physician.