Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
Intervention: Fludarabine; Velcade; Rituximab
Intervention description: Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.; Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy.; Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy.
Intervention MeSH terms: Rituximab; Fludarabine; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the effectiveness of fludarabine, Velcade, and
      rituximab treatment regimen in patients with relapsed or refractory follicular non-Hodgkin
      lymphoma.
    

Eligibility criteria:

        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.