Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
Condition: Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: Bexxar; Low Dose Methotrexate
Intervention description: Iodine I 131 tositumomab (Bexxar) is a radioimmunotherapy (RIT) drug. RIT is a treatment strategy designed to target radiation specifically to cancer cells by attaching a radioactive atom to a monoclonal antibody, an immune system protein that binds to a particular protein. The Iodine I 131 tositumomab (Bexxar) therapeutic regimen is delivered in two sets of intravenous infusions given about 7 days apart. Nonradioactive Tositumomab is given before both the "dosimetric" infusion and the "therapeutic" infusion to improve distribution of these doses throughout the body.; Methotrexate is an antifolate drug. It interferes with cells' ability to copy their DNA. This mainly affects cells that are dividing frequently, such as immune system cells and cancer cells. Methotrexate will be used in this study to try to prevent the occurrence of HAMA by limiting your body's ability to produce anti mouse antibodies.
Intervention MeSH terms: Methotrexate; Tositumomab I-131
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Previously Untreated, Advanced-Stage, Follicular Lymphoma

Summary:

      Patients with a type of non-Hodgkin lymphoma, called follicular lymphoma and have not yet had
      previous systemic treatment, such as chemotherapy or immunotherapy will be invited to
      participate. This research study is being conducted in order to evaluate the combination of
      lowdose methotrexate and Iodine I 131 tositumomab (Bexxar) with regards to whether the
      combination will reduce the occurrence of the HAMA (Human Anti-Mouse Antibody) response. HAMA
      is an immune reaction against the tositumomab protein. Symptoms arising from HAMA can range
      from a mild form, like a rash, to a more extreme and possibly life-threatening level. HAMA
      can also decrease the effectiveness of the treatment, or create a future reaction if a
      patient is given another treatment containing mouse antibodies. In addition to evaluating the
      occurrence of HAMA, this research study will also look at the short and long-term
      effectiveness of this combination in the treatment of lymphoma, as well as its safety.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have a histologically-confirmed diagnosis of follicular non-Hodgkin's
             B-cell lymphoma, grade 1-2 (grade 1 or grade 2 by WHO classification prior to 2009).

          2. Patients must have Ann Arbor Stage III or IV extent of disease after complete staging.

          3. Patients must have a willingness and ability to follow prescribed radiation
             precautions

          4. Patients must not have had any previous treatment for low-grade lymphoma including
             chemotherapy or radiation. They may be newly diagnosed or observed without treatment
             after diagnosis. Symptomatic and asymptomatic patients will be eligible.

          5. Patients must have a performance status of 0-2 on the Eastern Cancer Oncology Group
             (ECOG) scale and an anticipated survival of at least 3 months.

          6. Patients must have an absolute neutrophil count >1500 cells/mm3 and a platelet count
             >100,000 cells/mm3 within 14 days of study entry. These blood counts must be sustained
             without support of hematopoietic cytokines or transfusion of blood products.

          7. Patients must have adequate renal function (defined as serum creatinine <2.0) and
             hepatic function (defined as total bilirubin <1.5 x ULN and Aspartate Aminotransferase
             (AST) <3 x ULN) within 14 days of study entry.

          8. Patients must have bi-dimensionally measurable disease.

        Exclusion Criteria:

          1. Patients with follicular Grade 3a or 3b by WHO Classification.

          2. Patients with evidence of active infection requiring IV antibiotics at the time of
             study entry.

          3. Patients with New York Heart Association Class III or IV heart disease or other
             serious illness that would preclude evaluation.

          4. Patients with active obstructive hydronephrosis.

          5. Patients with prior malignancy other than lymphoma, except for adequately treated skin
             cancer, in situ cervical cancer, or other cancer for which the patient has been
             disease-free for 5 years.

          6. Patients with known HIV infection.

          7. Patients with known brain or leptomeningeal metastases.

          8. Patients who are pregnant or nursing. Patients of childbearing potential must undergo
             a pregnancy test within 7 days of study entry and methotrexate is not to be
             administered until a negative result is obtained. Males and females must agree to use
             effective contraception for 6 months following the radioimmunotherapy.

          9. Patients with previous allergic reactions to iodine. This does not include reacting to
             IV iodine-containing contrast materials.

         10. Patients with previous allergic reactions to methotrexate.

         11. Patients who were previously given any monoclonal antibody, regardless of species, for
             any condition.

         12. Detectable serum levels of HAMA.

         13. Patients who are concurrently receiving either approved or non-approved (through
             another protocol) anti-cancer drugs or biologics.