Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas and Extended Study to Determine the Safety and Efficacy of Coulter Clone® 131Iodine-B1 Radioimmunotherapy of Advanced Non-Hodgkin's Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab)
Intervention description: 131-I anti-B1 is the product of 131-I labeling of the anti-CD20 murine monoclonal antibody and the anti-B1 antibody itself is an intact IgG2a murine monoclonal antibody which has specificity far the CD20 antigen on human B cells. Anti-B1 is a clear, colorless liquid. 131-I labeling of the anti-B1 antibody will be carried out by iodogen technique. Trace labeling of the antibody will involve the labeling of approximately 1 to 3 mg of antibody with 5 mCi of 131-I.
Intervention MeSH terms: Tositumomab I-131; Antibodies; Antibodies, Monoclonal; Antibodies, Anti-Idiotypic
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tositumomab and/or Iodine I 131 Tositumomab; B-cell non-Hodgkin's lymphoma; Dose-limiting toxicity; Bexxar

Summary:

      Phase I/II, single-center, dose-escalation study of the safety, pharmacokinetics, dosimetry,
      and efficacy of TST/I-131 TST for the treatment of patients with chemotherapy-refractory or
      resistant low-grade, intermediate-grade, or high-grade B-cell lymphoma. Subjects received 1
      to 3 dosimetric doses followed by a therapeutic dose of TST/I-131 TST. Study BEX104526 was a
      follow-up study of the long-term safety and efficacy data from the surviving patients who
      completed at least 2 years of follow-up following administration of TST/I 131 TST on Study
      BEX104728.

      Dosimetric dose: Subjects received 1 to 3 dosimetric doses of TST/I-131 TST, followed by a
      therapeutic dose of TST/I-131 TST. Subjects received various doses of unlabeled TST (0, 95 or
      475 mg) to determine the dose of unlabeled TST that optimized the radiation dose delivered to
      the tumor by TST/I-131 TST. The unlabeled TST was followed by 5 milliCurie (mCi) of I-131
      TST. Serial whole body sodium iodide scintillation probe counts were obtained daily, for at
      least 5 days, in order to determine the rate of whole body clearance of radioactivity
      (residence time). The residence time was used to determine the radioactive clearance for the
      subject and the activity (in mCi) of I-131 required to deliver the desired TBD of radiation
      during the therapeutic dose. Because 475 mg was determined to be the optimal pre-dose of TST
      in the first subjects entered, the last 34 subjects received a single dosimetric dose that
      was preceded by an infusion of 475 mg of TST.

      Therapeutic dose: Groups of 3-6 subjects were enrolled at successively higher whole-body
      radiation dose levels beginning at a total body dose (TBD) of 25 centiGray (cGy). The TBD of
      each subsequent dose level was escalated by 10 cGy. Subjects who had undergone bone marrow
      transplantation (BMT) underwent a separate dose escalation (10 cGy TBD increase per dose
      level) beginning at a TBD level of 65 cGy. The MTD was defined as the highest dose level at
      which 0/3 or 1/6 subjects experienced dose-limiting toxicity (DLT). DLT was defined as
      follows:

      Any Grade 4 hematologic toxicity (National Cancer Institute [NCI] criteria) lasting greater
      than 7 days, or Any Grade 3 hematologic toxicity lasting greater than 2 weeks, or Any Grade 3
      or 4 nonhematologic toxicity Redosing. Subjects who achieved tumor regression were considered
      for re-dosing, using the original therapeutic dose of TST/I-131 TST, at the time the tumor
      was no longer shrinking in an attempt to upgrade their response.

      Retreatment. Subjects who achieved partial (PR) or complete response (CR) were considered for
      retreatment following relapse of their NHL, if progression occurred ≥6 weeks following the
      therapeutic dose. The original therapeutic dose of TST/I-131 TST was given unless a grade 2
      or greater toxicity had been encountered, in which case a reduced dose was administered for
      the repeat therapeutic dose.
    

Eligibility criteria:

        Inclusion Criteria

          -  Subjects had histologically-confirmed NHL.

          -  Subjects with low-, intermediate-, or high-grade histologies, according to the
             International Working Formulation.

          -  Subjects had relapsed after or had failed to respond to at least 1 prior chemotherapy
             regimen.

          -  Subjects had evidence that their tumor tissue expressed the CD20 antigen.

        Exclusion Criteria

          -  ≥25% bone marrow involvement.

          -  Absolute granulocyte count ≥1500 cells/mm3 or platelet count ≤100,000 platelets/mm3.

          -  Creatinine ≥2.0 mg/dL, bilirubin ≥2.0 mg/dL.

          -  Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment
             within 4 weeks of study entry.

          -  Active infection, collagen vascular disease, vasculitis, glomerulonephritis, New York
             Heart Association class II or IV heart disease and/or serious illness.

          -  Prior external beam radiation therapy such that the maximum tolerated dose level for
             any normal organ would be exceeded by additional irradiation.

          -  Pregnancy.

          -  Allergy to iodine or previous sensitization to mouse protein as documented by positive
             anti-mouse antibody ELISA test.

          -  Known brain metastases.