Study of Safety and Efficacy of a Sequential Regimen Consisting of Three Cycles of Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Tositumomab and Iodine I 131 Tositumomab
Intervention description: Tositumomab and Iodine I 131 Tositumomab
Intervention MeSH terms: Tositumomab I-131
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a single-arm, single institution, phase II study of fludarabine monophosphate
      followed by Iodine I 131 Tositumomab for patients with previously untreated, advanced-stage
      (stage III or IV) low-grade, transformed low-grade and follicular non-Hodgkin's lymphoma. The
      primary objective of the study will be to evaluate the safety of this treatment combination
      and the secondary endpoint will be to evaluate efficacy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be age 18 years or older.

          -  Patients must have a histologically-confirmed diagnosis of low-grade or follicular
             non-Hodgkin's B-cell lymphoma.

          -  Patients must have Ann Arbor stage III or IV extent of disease after completing
             staging.

          -  Patients must have bi-dimensionally measurable disease. At least one lesion must have
             both perpendicular diameters > 2 cm.

          -  Patients must have evidence that their tumor expresses the CD20 antigen by
             immunohistochemistry or flow cytometry.

          -  Patients must have no previous treatment for NHL.

          -  Patients must have a Karnofsky performance status of at least 60% and an anticipated
             survival of at least 3 months.

          -  Patients must have absolute granulocyte count greater than or equal to 1500 cells/mm3
             and a platelet count > 100,000 cells/mm3 within 14 days of study entry and not require
             sustained support with hematopoietic cytokines or transfusion of blood products.

          -  Patients must have adequate renal and hepatic function.

          -  Patients must sign IRB approved informed consent form(s) prior to study entry.

        Exclusion Criteria:

          -  Patients who received systemic steroids within 1 week of study entry, except patients
             on maintenance steroid therapy for a non-cancerous disease.

          -  Patients with evidence of active infection requiring intravenous antibiotics at the
             time of study entry.

          -  Patients with New York Heart Association class III or IV heart disease or other
             serious illness that would preclude evaluation.

          -  Patients with known HIV Infection.

          -  Patients with known brain or leptomeningeal metastases.

          -  Patients who are pregnant or nursing. Patients of childbearing potential must undergo
             a pregnancy test at screening and on the day fludarabine treatment is started.
             Treatment 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 iodine I
             131 tositumomab therapy.

          -  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.

          -  Patients with hypersensitivity to fludarabine.

          -  Patients who are receiving either approved or non-approved (through another protocol)
             anti-cancer drugs or biologics.

          -  Patients who are HAMA positive.

          -  Patients with previous allergic reaction to iodine. This does not include reacting to
             intravenous iodine containing contrast materials.

        Inclusion Criteria for Iodine I 131 Tositumomab Therapy

          -  Patients who completed 3 cycles of fludarabine.

          -  Patients must have absolute granulocyte count ≥ to 1500/mm3, platelet count of ≥
             100,000/mm3 (≥ 150,000/mm3 if > 25% bone marrow involvement at restaging), and not
             require sustained support with hematopoietic cytokines or transfusions with blood
             products.

          -  Patients must have adequate renal and hepatic function.

        Exclusion criteria for Antibody Therapy

          -  Patients with active obstructive hydronephrosis.

          -  Patients with evidence of active infection requiring intravenous antibiotics.

          -  Patients who are pregnant.