Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma

Inclusion Criteria:

- Must have histologically confirmed Follicular Non-Hodgkin Lymphoma (Grade I, II, or IIIa)

- Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥2 cm with conventional techniques or as >1 cm with spiral CT scan) and obtained by imaging within 30 days prior to registration for protocol therapy.

- Must have received at least one prior therapeutic regimen, but no more than three prior regimens of conventional cytotoxic therapy. NOTE: Prior recipients of stem cell transplantation will be included, with the preparative cytoreductive and high-dose therapies counted collectively as one prior therapy.

- Must be off all cytotoxic chemotherapy for at least four weeks prior to registration for protocol therapy (6 weeks for BCNU or mitomycin C).

- Patients are allowed to have received one course of prior radioimmunotherapy (RIT: either tositumomab or ibritumomab). NOTE: Radioimmunotherapy must be completed at least 12 weeks prior to registration for protocol therapy with recovery to baseline of ANC and platelets.

- Prior fludarabine, Velcade or rituximab is allowed as long as therapy is completed at least 30 days prior to registration for protocol therapy. Patients may be refractory (defined as not responding or demonstrating progressive disease in <6 months) to prior rituximab. Patients may not be refractory to prior fludarabine or Velcade.

- Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed and for 30 days following protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

- Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Patients are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (no menses for at least 12 months).

- Females must not be breastfeeding.

- Males must agree to use an acceptable method of contraception for the duration of the study.

Exclusion Criteria:

- No current active CNS metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 7 days prior to registration for protocol therapy. NOTE: Patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 30 days prior to registration for protocol therapy.

- No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 6 prostate cancers, or other cancer for which the subject has been disease-free for at least 3 years.

- No treatment with any investigational agent within 30 days prior to registration for protocol therapy.

- Prior radiation therapy is allowed to < 25% of the bone marrow. NOTE: No radiation therapy within 30 days prior to registration for protocol therapy.

- No clinically significant infections as judged by the treating investigator.

- No active HIV, hepatitis B or hepatitic C infection.

- No cerebrovascular accident (CVA) within 6 months of study enrollment.

- No psychiatric illness/social situations that would limit compliance with study requirements.

- No history of hypersensitivity to Velcade, boron or mannitol.

- No peripheral neuropathy grade > 1.