Iodine-131 Anti-B1 Antibody (Tositumomab and Iodine I 131 Tositumomab) for Previously Untreated, Advanced-stage, Low Grade Non-Hodgkin's Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Tositumomab and Iodine I 131 Tositumomab (Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody)
Intervention description: Dosimetric Dose: 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 5 mCi (35 mg) of Iodine-131 Anti-B1 Antibody infused over 30 minutes (inclusive of a 10-minute flush).
Therapeutic Dose: Seven to 14 days after the dosimetric dose, 450 mg of Anti-B1 Antibody infused over 70 minutes (inclusive of a 10-minute flush), immediately followed by the patient-specific milliCurie activity (35 mg) of Iodine-131 Anti-B1 Antibody to deliver a total body dose (TBD) of 75 cGy infused over 30 minutes (inclusive of a 10-minute flush). Obese patients were dosed based upon 137% of their calculated lean body mass.
Intervention MeSH terms: Iodine; Tositumomab I-131; Antibodies; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radioimmunotherapy; Anti-B1 Antibody and Iodine-131 Anti-B1 Antibody; Tositumomab and Iodine I 131 Tositumomab; non-Hodgkin's Lymphoma; Bexxar

Summary:

      This is a single-arm, single-institution, phase II study of Iodine-131 Anti-B1 Antibody for
      patients with previously untreated, advanced-stage (stage III or IV) low-grade non-Hodgkin's
      B-cell lymphoma. A total of 75-80 patients will be enrolled.

      Patients will undergo two phases of the study. In the first phase, termed the "dosimetric
      dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450 mg) over 70
      minutes (including a 10-minute flush) immediately followed by a 30-minute infusion (including
      a 10-minute flush) of Anti-B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of
      Iodine-131. Whole body gamma camera scans will be obtained 5 to 8 times between Days 0 and 7
      following the dosimetric dose. Using the dosimetric data from 3 imaging timepoints (the
      imaging timepoints to be used in decreasing order of preference depending on availability of
      data are Days 0, 3, and 7; Days 0, 4, and 7; Days 0, 3 and 6; Days 0, 4, and 6; Days 0, 2,
      and 7; and Days 0, 2, and 6), a patient-specific dose of Iodine- 131 to deliver the desired
      total body dose of radiotherapy will be calculated. In the second phase, termed the
      "therapeutic dose", patients will receive a 70-minute infusion (including a 10-minute flush)
      of unlabeled Anti-B1 Antibody (450 mg) immediately followed by a 30-minute infusion
      (including a 10-minute flush) of Anti-B1 Antibody (35 mg) labeled with the patient-specific
      dose of Iodine-131 to deliver a whole body dose of 75 cGy. Patients who are obese will be
      dosed based upon 137% of their calculated lean body mass. Patients will be treated with
      either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide
      tablets starting at least 24 hours prior to the first infusion of the Iodine-131 Anti-B1
      Antibody (i.e., dosimetric dose) and continuing for 14 days following the last infusion of
      Iodine-131 Anti-B1 Antibody (i.e., therapeutic dose).

      The primary endpoint of the study is the determination of the response rate with Iodine-131
      Anti-B1 Antibody in previously untreated patients with low-grade non-Hodgkin's lymphoma
      (NHL). The secondary endpoints include duration of response, safety, radiation dosimetry, and
      the predictive value of detection of the presence or absence minimal residual disease by
      molecular techniques on response duration.
    

Eligibility criteria:

        Inclusion Criteria

          -  Patients must have a histologically confirmed diagnosis of lowgrade non-Hodgkin's
             B-cell lymphoma. The following low-grade histologies are included: small lymphocytic
             (with or without plasmacytoid differentiation); follicular, small cleaved; follicular,
             mixed small cleaved and follicular large cell (less than 50% large cell component);
             and monocytoid B-cell lymphoma.

          -  Patients must have evidence that their tumor tissue expresses the CD20 antigen.
             Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with
             L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity
             with Anti-B1 Antibody (Coulter Clone®) or similar commercially available CD20 antibody
             (>50% of tumor cells are positive) or evidence of CD20 positivity by flow cytometry
             (>50% of tumor cells are positive) are acceptable evidence of CD20 positivity. Testing
             of tumor tissue from any time in the course of the patient's disease is acceptable.

          -  Patients must have Ann Arbor stage III or IV extent of disease after complete staging.

          -  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.

          -  Patients must have a performance status of at least 60% on the Karnofsky Scale and an
             anticipated survival of at least 3 months.

          -  Patients must have an absolute neutrophil count (ANC) >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.

          -  Patients must have 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 14 days of study entry.

          -  Patients must have bi-dimensionally measurable disease. At least one lesion must be ≥2
             x 2 cm (by computed tomography [CT] scan).

          -  Patients must be at least 18 years of age.

          -  Patients must give written informed consent and sign an IRB- approved informed consent
             form prior to study entry.

        Exclusion Criteria

          -  Patients with more than an average of 25% of the intratrabecular marrow space involved
             by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days
             of study entry. Bilateral posterior iliac crest core biopsies are required if the
             percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy. The
             mean of bilateral biopsies must be no more than 25%.

          -  Patients with evidence of active infection requiring intravenous (IV) 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 active obstructive hydronephrosis.

          -  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 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 within 7 days of study entry and radiolabeled antibody 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.

          -  Patients with previous allergic reactions to iodine. This does not include reacting to
             IV iodine-containing contrast materials.

          -  Patients who were previously given any monoclonal or polyclonal antibodies of any
             non-human species for either diagnostic or therapeutic purposes. This includes
             engineered chimeric and humanized antibodies.

          -  Patients who are concurrently receiving either approved or nonapproved (through
             another protocol) anti-cancer drugs or biologics.