Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma

Multicenter, Pivotal Phase III Study of Iodine-131 Anti-B1 Antibody (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies

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.

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.