Safety and Efficacy Study of Iodine-131 Anti-B1 Antibody Plus CHOP For Untreated Mantle Cell Lymphoma
Condition: Lymphoma, Mantle-Cell
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Tositumomab and Iodine I 131 Tositumomab followed by CHOP
Intervention description: Patients will receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of Tositumomab (35 mg) containing 5 mCi of Iodine-131 (dosimetric dose). Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4; and Day 6 or 7 following the dosimetric dose. Patients will then receive an infusion of unlabeled Tositumomab (450 mg) followed by an infusion of 35 mg Tositumomab containing a patient-specific dose of Iodine-131 calculated to deliver a 75 cGy total body radiation dose (therapeutic dose). Patients who have platelet counts of 100,000-149,000 cells/mm3 will receive 65 cGy; obese patients will be dosed based upon 137% of their lean body mass. Patients will be treated with a thyroid blocking agent 24 hours prior to the dosimetric dose and continuing for 14 days following the therapeutic dose. Approximately 13 weeks following the therapeutic dose, CHOP will be administered every 21 days for a total of 6 cycles.
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: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP); Tositumomab; Tositumomab and Iodine I-131 tostumomab; Bexxar; Iodine-131 Anti-B1 Antibody; Mantle Cell; radioimmunotherapy

Summary:

      The primary efficacy endpoint of this study is to determine the duration of response of the
      sequential administration of Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP for
      patients with previously untreated Mantle Cell Lymphoma (MCL). The secondary efficacy
      endpoints for this study are to determine the response rate, confirmed response rate,
      complete response rate, confirmed complete response rate, duration of response for confirmed
      responders, duration of response for complete responders, duration of response for confirmed
      complete responders, progression-free survival, time to treatment failure, and the predictive
      value of detection of minimal residual disease by molecular techniques on response duration.
      The pharmacokinetic endpoint is to determine the total body residence time of Iodine-131
      Anti-B1 Antibody following the dosimetric dose. The safety endpoints are to determine the
      incidence of adverse experiences, hematologic toxicity, (e.g., nadir, time to nadir, and time
      to recovery), use of supportive care, percent of patients converting to human anti-murine
      antibody (HAMA) positivity, the effects of Iodine-131 Anti-B1 Antibody on the growth and
      function of hematopoietic progenitor cells, and survival of patients with previously
      untreated MCL treated with Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a confirmed initial diagnosis of mantle cell non-Hodgkin's lymphoma
             by histology according to the WHO classification .

          -  Patients must have Ann Arbor bulky stage II, stage III, or stage IV disease at
             diagnosis. Bulky stage II disease 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.

          -  Patients must have less than an average of 25% of the intratrabecular marrow space
             involved by NHL in bilateral bone marrow biopsy specimens as assessed microscopically
             at study entry. A unilateral bone marrow biopsy demonstrating <10% involvement with
             NHL is also adequate.

          -  Patients 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. This must be performed within 42 days of study entry.

          -  Patients must have a performance status of at least 60% on the Karnofsky Performance
             Scale and an anticipated survival of at least 3 months.

          -  Patients must have an ANC greater than or equal to 1500 cells/mm3 and a platelet count
             greater than or equal to 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.

          -  Patients 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.

          -  Patients must have bi-dimensionally measurable disease. At least one lesion must be
             greater than or equal to 2.0 x 2.0 cm by computerized tomography scan.

          -  Females of childbearing potential must have a negative serum pregnancy test within 7
             days prior to study enrollment.

          -  Patients must have a cardiac left ventricular ejection fraction of greater than or
             equal to 50% by ventriculography or echocardiogram.

        Exclusion Criteria:

          -  Patients who have received prior chemotherapy, biologic therapy, steroids, or
             radiation therapy as treatment for their MCL

          -  Patients with active obstructive hydronephrosis

          -  Patients with serious illness that would preclude evaluation

          -  Patients 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 with known HIV infection

          -  Patients who are HAMA positive

          -  Patients with known brain or leptomeningeal metastases.

          -  Patients who are pregnant or breastfeeding. Males and females must agree to use a
             contraceptive method while on study and for 6 months after receiving Iodine-131
             Anti-B1 Antibody.

          -  Patients with active infection requiring IV anti-infectives at the time of study
             enrollment.