Rituximab, Fludarabine, Mitoxantrone, Dexamethasone (R-FND) Plus Zevalin for High-Risk Follicular Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: Fludarabine; Mitoxantrone; Rituximab; Zevalin; Dexamethasone
Intervention description: 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4.; 10 mg/m^2 IV over 5-30 minutes on Day 2.; 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total).; 0.3 mCi/kg IV after 4 cycles of R-FND.; 20 mg by mouth (PO) or IV daily on Days 2-6.
Intervention MeSH terms: Dexamethasone; Rituximab; Fludarabine; Fludarabine phosphate; Mitoxantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Follicular Lymphoma; Zevalin; Ibritumomab Tiuxetan; IDEC-Y2B8; Fludarabine; Fludara; Dexamethasone; Mitoxantrone; Rituximab; Rituxan; R-FND; Fludarabine Phosphate; Decadron

Summary:

      The goal of this clinical research study is to learn if chemotherapy given with rituximab,
      followed by Ibritumomab tiuxetan (Zevalin), and then followed by rituximab can help to
      control lymphoma. The safety of this treatment schedule will also be studied.

      Objectives:

        1. To assess whether the time to progression for these high-risk patients can be prolonged
           to a median of 36 months, compared to the historical expectation of approximately 24
           months.

        2. To assess the tolerance and efficacy of Y2B8 (Zevalin) after R-FND (rituximab,
           fludarabine, mitoxantrone, dexamethasone) in patients with high-risk stage III-IV
           follicular lymphoma

        3. To assess overall response, failure-free survival, and survival of this strategy
           compared to our historical experience with FND (fludarabine, mitoxantrone,
           dexamethasone) alone or R-FND

        4. To assess the tolerance and efficacy of maintenance therapy with rituximab.

        5. To maximize the 12-month molecular remission rate for patients with high-risk stage
           III-IV follicular lymphoma

        6. to correlate the results of quantitative PCR assay with classical PCR and with clinical
           outcome
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with high-risk Ann Arbor stage III-IV follicular lymphoma. High-risk is
             defined by advanced stage (III or IV), plus any 2 of the following features: age 60 or
             greater; elevated LDH; Hgb < 12; or number of involved nodal sites 5 or more .

          2. Patients will be previously untreated.

          3. Adequate organ function.

          4. Follicular lymphoma, grade 3 (follicular large cell lymphoma): If eligible for a
             current large cell lymphoma protocol, that alternative protocol is recommended,
             particularly grade 3b or FLCL patients characterized as large non-cleaved cell.
             However, both FND and rituximab have established efficacy in FLCL, so if a patient is
             not eligible for a protocol for aggressive lymphoma (e.g., because of SCCL in the
             marrow), then registration on this trial is permitted.

          5. Biopsy or fine-needle aspiration (FNA) material is strongly recommended for bcl-2
             studies to verify rearrangement status of all patients who are designated "germline".
             (see section 6.4). For other patients, tissue availability is desirable but not
             mandatory.

          6. Patients must have a performance status of Zubrod 3 or better

          7. Patients must have adequate renal and hepatic function (creatinine < 2mg%; bilirubin <
             2 mg%). Patients with renal or liver dysfunction due to organ infiltration by lymphoma
             may be eligible after discussion with the study chairman.

          8. Patients may not receive other concurrent chemotherapy, radiotherapy, or
             immunotherapy.

          9. Patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study in keeping with the policies of the hospital.

        Exclusion Criteria:

          1. Patients who are unable or unlikely to be able to adhere to the treatment plan or to
             return to Houston for follow-up visits because of geographical, economic, emotional,
             or social considerations are not eligible for this study. Note: some follow-up care
             may be provided by outside physicians as long as the MD Anderson Cancer Center (MDACC)
             protocol for outside physician participation is strictly adhered to.

          2. Patients with an absolute peripheral granulocyte count of < 1,000 and platelet count <
             100,000 unless due to marrow infiltration or hypersplenism.

          3. Patients with organ dysfunction, including bilirubin of > 2 mg% or serum creatinine
             level > 2 mg%, unless the alteration is due to lymphoma.

          4. Patients with HIV infection should not be registered on this protocol.

          5. Patients with an antecedent malignancy whose prognosis is poor (< 90% probability of
             surviving for 5 yrs).

          6. All patients should have a cardiac ejection fraction of 50% or more by
             echocardiography or multiple gated acquisition scan (MUGA).

          7. Patients who will not accept transfusions of blood products or supportive care
             measures such as antibiotics are not eligible for this study.

          8. Female patients must not be pregnant or lactating, and men and women of reproductive
             potential must follow accepted birth control methods.

          9. Patients who have received prior murine antibody therapy will be excluded.

         10. Patients with evidence of active or prior infection of Hepatitis B are excluded.
             (Note: Persons vaccinated for Hepatitis B who have + antibodies are not excluded).