Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Tositumomab and Iodine I 131 Tositumomab
Intervention description: Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST, of which 1-2 mg had been labeled with 5 mCi of Iodine-131) infused over 30 minutes (inclusive of a 10-minute flush).
Therapeutic Dose: 7 to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST labeled with enough Iodine-131 to administer the specified whole body radiation dose determined for the subject) infused over 30 minutes (inclusive of a 10-minute flush). The desired total body dose was 65 cGy for subjects with a baseline platelet count of 100,001-149,999/mm3 and 75 cGy for patients with a baseline platelet count ≥150,000/mm3. Obese patients received an attenuated dose by not including subject mass over 137% of their calculated lean body mass in their calculated lean body mass in the dose calculation.
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: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: non-Hodgkin's Lymphoma; radioimmunotherapy; NHL; Bexxar; lymphoma; Tositumomab

Summary:

      The results from Phase 1/2 (RIT-I-000) and Phase 2 (RIT-II-001) studies of Tositumomab and
      Iodine I 131 Tositumomab (TST/I-131 TST) demonstrated that TST/ I-131 TST produced a high
      response rate in patients with chemotherapy-relapsed/refractory, low-grade or transformed
      low-grade Non-Hodgkin's Lymphoma (NHL). On the basis of these results this study was designed
      to compare the efficacy of TST/ I-131 TST to the last qualifying chemotherapy regimen in
      patients with chemotherapy-refractory, low-grade or transformed low-grade NHL.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects ≥18 years of age with histologically confirmed at initial
             diagnosis, previously treated (at least 2 prior chemotherapy regimens), low-grade NHL
             or low-grade lymphoma that had transformed to intermediate- or high-grade histology.

        Exclusion Criteria:

          -  Subjects 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 intratrebecular space involved exceeds 10% in a unilateral biopsy. The
             mean of bilateral biopsies must be no more than 25%.

          -  Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment
             within 4 weeks prior to study entry or persistent clinical evidence of toxicity.

          -  Prior stem cell transplant.

          -  Active obstructive hydronephrosis.

          -  Evidence of active infection requiring intravenous (IV) antibiotics at the time of
             study entry.

          -  New York Heart Association Class III or IV heart disease or other serious illness that
             would preclude evaluation.

          -  Prior malignancy other than lymphoma, except for adequately treated skin cancer, in
             situ cervical cancer, or other cancer for which the subject has been disease-free for
             5 years.

          -  Known HIV infection.

          -  Known brain or leptomeningeal metastases.

          -  Subjects who are pregnant or nursing.

          -  Previous allergic reactions to iodine. This does not include reactions to intravenous
             iodine-containing contrast materials.

          -  Prior exposure to monoclonal or polyclonal antibodies of any non-human species for
             either diagnostic or therapeutic purposes, including engineered chimeric and humanized
             antibodies.

          -  Prior radioimmunotherapy.

          -  Progressive disease within 1 year of irradiation arising in a field that has been
             previously irradiated with >3500 cGy.

          -  Current use of either approved or non-approved (through another protocol) anti-cancer
             drugs or biologics

          -  De novo intermediate- or high-grade lymphoma.