A Study Of Pharmacokinetics, Whole Body And Organ Dosimetry, And Biodistribution Of Fission-Derived Iodine I 131 Tositumomab (BEXXAR®) For Patients With Previously Untreated Or Relapsed Follicular Or Transformed Non-Hodgkin's Lymphoma
Condition: Lymphoma, Follicular
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
Intervention: Follicular Lymphoma
Intervention description: For subjects with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bexxar; tositumomab and iodine I 131 tositumomab therapeutic regiment; fission; Non-Hodgkin's lymphoma; Iodine I 131 Tositumomab; pharmacokinetics; tellurium

Summary:

      Patients will receive a standard 5 mCi dosimetric dose of fission-derived Iodine I 131
      Tositumomab. Pharmacokinetic data for the primary endpoint analysis will be derived from
      testing done on blood samples drawn at 12 timepoints over the first 7 days following
      administration of the dosimetric dose. Whole body gamma camera images will be obtained on six
      days following the dosimetric dose. Organ and tumor dosimetry data will be generated from
      gamma camera counts of specific organs and tumor. All scans will be examined by an
      independent review panel to evaluate biodistribution of the radionuclide.

      Using the dosimetric data from three of the six imaging time points and the patient's weight,
      a patient-specific activity (mCi) of Iodine-131 will be calculated to deliver the desired
      total body dose of radiation (75 cGy). Patients will receive an infusion of unlabeled
      Tositumomab (450 mg) immediately followed by an infusion of the patient specific dose of
      tellurium-derived Iodine I 131 Tositumomab (35 mg) to deliver a total body dose (TBD) of 75
      cGy. Patients will be followed closely obtaining safety information during the post-treatment
      period, and for response and safety at 3,6,and 12 months during the first year, annually
      thereafter up to five years, and annually for additional safety and outcomes information up
      to 10 years.
    

Eligibility criteria:

        Inclusion criteria

          1. At least 18 years of age

          2. A histologically confirmed diagnosis of the following:

             Follicular lymphoma, Grade 1, 2, or 3 or diffuse large cell lymphoma concurrent with
             or following the diagnosis of follicular lymphoma (World Health Organization/Revised
             European-American Lymphoma [WHO/REAL] classification).

             International Working Formulation histological equivalents included:

             Follicular, small-cleaved; Follicular, mixed small-cleaved and large-cell; Follicular
             large-cell; or Transformed diffuse large-cell lymphoma following or concurrent with a
             diagnosis of follicular lymphoma.

          3. Stage III or IV disease at the time of study entry (based on Ann Arbor Staging
             Classification)

          4. Previously untreated or recurrent lymphoma after no more than 4 prior qualifying
             therapy regimens; steroids alone, as treatment for lymphoma, not considered a
             treatment regimen

          5. Performance status of at least 70% on the Karnofsky Performance Scale and an
             anticipated survival of at least 3 months.

          6. Bi dimensionally measurable disease with at least one lesion measuring greater than or
             equal to 2.0 cm x 2.0 cm (greater than or equal to 4.0 cm2) by computed tomography
             (CT) scan

          7. Absolute B lymphocyte count (as determined by CD19 reactivity [flow cytometric
             determination of CD19+ B lymphocyte count]) of 30 to 350 cell/mm3 within 21 days prior
             to study enrollment

          8. Absolute neutrophil count greater than or equal to 1500 cells/mm3; platelet count
             greater than or equal to 150,000/mm3; and hemoglobin greater than or equal to 10 g/dL
             within 21 days prior to study enrollment; blood products and/or growth factors not
             taken within 4 weeks prior to blood draw

          9. Adequate renal function, defined as serum creatinine <1.5 x upper limit of normal
             (ULN), and hepatic function, defined as total bilirubin <1.5 x ULN and aspartate
             transaminase (AST) <5 x ULN, within 21 days of study enrollment

         10. HAMA negative within 21 days prior to study enrollment

         11. Signed IRB approved consent form prior to any study-specific procedures being
             implemented

        Exclusion criteria

          1. Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone
             marrow biopsy specimens as assessed microscopically within 90 days of study
             enrollment; a unilateral bone marrow biopsy was adequate; marrow core was greater than
             or equal to 2.0 cm in length

          2. Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for
             NHL within 28 days prior to study enrollment; subjects receiving low doses of steroids
             for non neoplastic disease acceptable to enter this study ("Low dose steroids" was
             defined as less than or equal to 10 mg of prednisone or equivalent per day.)

          3. Prior rituximab therapy within 120 days prior to study enrollment

          4. Prior radioimmunotherapy

          5. Prior splenectomy

          6. Splenomegaly defined as spleen mass greater than 700 grams, where splenic mass was
             defined as follows:

             Spleen mass = л(X x Y x Z)/6 Where X and Y are the greatest perpendicular diameters in
             cm on any single CT scan slice, and Z is the number of CT scan slices upon which the
             spleen is visible times the slice thickness in cm

          7. Bulky disease as defined as any uni-dimensional measurement of lymphomatous mass
             exceeding 7 cm

          8. Prior malignancy other than lymphoma, except for adequately treated skin cancer, in
             situ cervical cancer, or other cancer for which the subject had a generally accepted
             risk of recurrence less than 20%

          9. Central nervous system involvement by lymphoma

         10. Evidence of active infection requiring IV antibiotics at the time of study enrollment

         11. Known human immunodeficiency virus (HIV) infection

         12. New York Heart Association Class III or IV heart disease or other serious illness that
             would preclude evaluation.

         13. Active obstructive hydronephrosis

         14. Evidence of clinically significant ascites or pleural effusion observed on screening
             physical examination or baseline CT scan

         15. Prior myeloablative therapy

         16. History of failed stem cell collection

         17. Pregnant or nursing subjects (Subjects of childbearing potential had to have a
             negative serum pregnancy test within 21 days of study enrollment. Males and females of
             childbearing age had to agree to use effective contraception for up to 12 months after
             the radioimmunotherapy.)