Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
Intervention: Tositumomab and Iodine I 131 Tositumomab; Rituximab
Intervention description: Dosimetric dose: 450 mg Tositumomab infused over 1 hour followed by 5 mCi I 131 Tositumomab infused over 20 minutes
Therapeutic dose: 450 mg Tositumomab infused over 1 hour followed by Individualized mCi activity of I 131 Tositumomab (35 mg) infused over 20 minutes.; Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.
Intervention MeSH terms: Iodine; Rituximab; Tositumomab I-131; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rituximab; tositumomab and iodine I 131 tositumomab; non-Hodgkins lymphoma; radioimmunotherapy; anti-B1 antibody; Bexxar; NHL; Tositumomab

Summary:

      Comparison of rituximab versus Iodine I 131 Tositumomab Therapeutic Regimen (Tositumomab and
      Iodine I 131 Tositumomab or the Bexxar Therapeutic Regimen, formerly called Iodine-131
      Anti-B1 Antibody) in subjects with follicular non Hodgkins B cell lymphoma. 506 subjects will
      be enrolled at 30 to 40 sites in the US, Canada, and Europe. Subjects will be randomly
      assigned to one of two treatment arms. In Arm A, subjects will receive 375 milligrams/meter2
      (mg/m2 )of rituximab, given as an intravenous (IV) infusion once weekly for 4 weeks. In Arm
      B, subjects will undergo a two-phase treatment. In the first phase, termed the "dosimetric
      dose," subjects will receive an infusion of unlabeled Tositumomab (450 mg) immediately
      followed by an infusion of 5 millicuries (mCi) (0.18 gigabecquerel [GBq]) of Iodine 131
      Tositumomab (35 mg). Whole body gamma camera scans will be obtained three times (Day 0; Day
      2, 3, or 4; and Day 6 or 7) following the dosimetric dose. The information derived from the
      scans will enable a patient specific dose to be calculated to deliver the desired total body
      dose of radiation (65 or 75 centigray [cGy]). In the second phase, termed the "therapeutic
      dose," subjects in Arm B will receive an infusion of unlabeled Tositumomab (450 mg)
      immediately followed by an infusion of the subject specific activity of Iodine 131-conjugated
      Tositumomab (35 mg). Thyroid blockade will be implemented 24 hours prior to the dosimetric
      dose and continued for 14 days following the therapeutic dose. Subjects on study will be
      followed for response and safety at Week 7, Week 13, and every three months for the first and
      second year, every six months for the third year, and then annually for the forth and fifth
      years; and then for vital status, additional therapy, and long term safety events through
      year ten. Follow Up after subsequent NHL therapy will be carried out to assess tolerance of
      next anti-lymphoma therapy, development of myelodysplasia (MDS)/acute myelogenous leukemia
      (AML), HAMA or hypothyroidism, unexpected safety issues, and death.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically confirmed diagnosis of follicular lymphoma

          -  Recurrent lymphoma after one or two qualifying therapy regimen(s)

          -  Patients must not have progressed within 4 weeks of their last chemotherapy dose

          -  Rituximab may have been used once as a single agent, in one continuous course of 4-8
             weekly infusions (10-week period), or in combination with chemotherapy in a single
             prior treatment

          -  Patients whose prior therapy includes rituximab must have had a 6 month or greater
             response duration following the rituximab-containing regimen.

          -  Performance status of at least 70% on the Karnofsky Scale and an anticipated survival
             of at least three months

          -  Adequate absolute neutrophil count and platelet count within 21 days of study entry
             without support of blood products/growth factors

          -  Adequate renal function and adequate hepatic within 21 days of study entry

          -  Measurable disease, with at least one lesion measuring >/=2.0 cm x 2.0 cm by CT scan

          -  Human Anti Mouse Antigen negative

          -  Written informed consent prior to study entry

        Exclusion criteria:

          -  Histologic transformation to diffuse, large cell lymphoma.

          -  History of more than one course of Rituximab

          -  Disease limited to single lymph node or single group of nodes

          -  Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen.

          -  Active infection requiring IV antibiotics at the time of study entry

          -  New York Heart Association Class III/IV heart disease

          -  Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks

          -  Any prior radioimmunotherapy

          -  Prior history of malignancy other than lymphoma (except for treated basal cell,
             squamous cell skin cancer, in situ cervical cancer, or other cancer that is
             disease-free for 5 years)

          -  Known HIV infection

          -  Hepatitis B positive

          -  Known central nervous system involvement