Open Label Multicenter Study of CVP Followed by Iodine-131 Anti-B1 Antibody for Subjects With Untreated Low-Grade Non Hodgkin's Lymphoma.
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab.
Intervention description: cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab. CVP will be repeated every 21 days for a total of six cycles. tositumomab and iodine I 131 tositumomab will begin within 56 days following the first day of the sixth cycle of CVP. Patient will undergo two dosing phase for the tositumomab and iodine I 131 tositumomab therapy.
Intervention MeSH terms: Tositumomab I-131
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkin's Lymphoma; tositumomab and iodine I 131 tositumomab; Bexxar; cycolophosphamide, vacristine, and pednisone

Summary:

      This is a phase II, open-label, multicenter study of the efficacy and safety of sequential
      administration of CVP x 6 followed by tositumomab and iodine I 131 tositumomab (formerly
      referred to as tositumomab and iodine I 131 tositumomab). All patients who complete three
      cycles of CVP, regardless of response, will be eligible for treatment with tositumomab and
      iodine I 131 tositumomab. Subjects who have rapidly progressive disease prior to completing
      three cycles of CVP may be removed from study.

      In order to proceed to tositumomab and iodine I 131 tositumomab therapy, patients must have
      completed six cycles of CVP within 20 weeks as described. Patients may proceed to Iodine-131
      Anti-B1 Antibody if they have progressive disease documented at the response evaluation
      following 6 cycles of CVP. In addition, patients must still meet the eligibility inclusion
      exclusion criteria based upon the week 20 assessments, as applicable. Patients must also have
      an average of ≤25% bone marrow involved by NHL to receive treatment with tositumomab and
      iodine I 131 tositumomab. The dosimetric dose of tositumomab and iodine I 131 tositumomab
      must be given within 28 days of the response evaluation following CVP and no later than 56
      days from the first day of the sixth cycle of CVP.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have a histologically confirmed initial diagnosis of low-grade
             non-Hodgkin's B-cell lymphoma according to the International Working Formulation (IWF)
             (32) (i.e., small lymphocytic with or without plasmacytoid differentiation; follicular
             small cleaved cell; or follicular, mixed small cleaved and large cell).

          -  Subjects must have Ann Arbor Stage III, Stage IV, or bulky Stage II disease at
             diagnosis. Bulky Stage II is defined as a mediastinal mass greater than one-third of
             the maximum chest diameter, or any other mass greater than or equal to 10 cm in
             maximum diameter.

          -  Subjects 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
             or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20
             positivity. Testing of tumor tissue from any time in the course of the patient's
             disease is acceptable.

          -  Subjects must have a performance status of at least 60% on the Karnofsky Performance
             Scale and an anticipated survival of at least 3 months.

          -  Subjects must have an ANC≥1500 cells/mm3 and a platelet count ≥100,000 cells/mm3
             within 14 days of study enrollment. These blood counts must be sustained without
             support of hematopoietic cytokines or transfusion of blood products.

          -  Subjects must have adequate renal function (defined as serum creatinine <1.5 times the
             upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the
             upper limit of normal and AST <5 times the upper limit of normal) within 14 days of
             study enrollment.

          -  Subjects must have bi-dimensionally measurable disease. At least one lesion must be
             ≥2.0x2.0 cm by computerized tomography scan.

          -  Subjects must be at least 18 years of age.

          -  Subjects of childbearing potential must have a negative serum pregnancy test within 7
             days prior to study enrollment.

          -  Subjects must give written informed consent and sign an IRB-approved informed consent
             form prior to study enrollment.

        Exclusion Criteria:

          -  Subjects who have received prior chemotherapy, biologic therapy, steroids, or
             radiation therapy as treatment for their NHL.

          -  Subjects with active obstructive hydronephrosis.

          -  Subjects with New York Heart Association class III or IV heart disease or other
             serious illness that would preclude evaluation.

          -  Subjects 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 who have been disease-free of another cancer for
             greater than 5 years must be carefully assessed at the time of study entry to rule out
             recurrent disease.

          -  Subjects with known HIV infection.

          -  Subjects who are HAMA positive.

          -  Subjects with known brain or leptomeningeal metastases.

          -  Subjects who are pregnant or breastfeeding. Males and females must agree to use a
             contraceptive method from enrollment to 6 months after receiving Iodine 131 Anti B1
             Antibody.

          -  Subjects with active infection requiring IV anti-infectives at the time of study
             enrollment.

          -  Subjects with intermediate- or high-grade NHL.