Rituximab, Cyclophosphamide, Bortezomib, and Prednisone in Patients With Stage III/IV FL or MZL

OUTLINE:

- Induction therapy: Patients receive rituximab IV and cyclophosphamide IV over 30 minutes
on day 1, bortezomib IV on days 1 and 8, and oral prednisone once daily on days 1-5.
Treatment repeats every 21 days for up to 8 courses in the absence of disease
progression or unacceptable toxicity. Patients then proceed to maintenance therapy.

- Maintenance therapy: Patients receive rituximab IV on days 1, 8, 15, and 22. Treatment
repeats every 6 months for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study therapy, patients are followed every 4 months for 1 year, every 6
months for 2 years, and then annually thereafter.

Inclusion Criteria

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

- Histologically confirmed, untreated follicular lymphoma (FL) grade I, II or marginal
zone lymphoma (MZL) Stage III or IV

- Presence of measurable or evaluable disease

- Age >17 years old

- Patients must have normal organ and marrow function as defined below, within 14 days
of enrollment:

- Serum bilirubin < 2.0 mg/dL

- serum creatinine < 2 mg/dL unless due to lymphoma

- Absolute Neutrophil Count (ANC) >1000/mm3

- Platelets >100,000/mm3 unless due to lymphoma

- Aspartate Transaminase (AST), Alanine Aminotransferase (ALT) and Alkaline
phosphatase < 3x the upper limit of normal

- Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, 3

- No prior therapy for the FL or MZL including chemotherapy, single agent rituximab and
radiation therapy

- Female subject is either post-menopausal or surgically sterilized or willing to use an
acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.

- Male subject agrees to use an acceptable method for contraception for the duration of
the study.

Exclusion Criteria

- Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure (see Appendix 5), uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities.

- Patient has hypersensitivity to boron or mannitol.

- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum β-human chorionic gonadotropin
(β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.

- Patient has received other investigational drugs with 14 days before enrollment

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- History of HIV infection (testing not required)

- Concurrent or previous malignancy whose prognosis is poor (< 90% probability of
survival at 5 years) or those who are actively being treated for a second malignancy.