Study of Iodine 131 Anti B1 Antibody for 1st or 2nd Relapsed Indolent B-Cell Lymphomas or B-Cell Lymphomas That Have Transformed to a More Aggressive Histology
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
Intervention: tositumomab and Iodine I 131 tositumomab (anti-B1 antibody)
Intervention description: For the treatment of 1st or 2nd relapsed indolent B cell lymphomas or B cell lymphomas that have transformed to a more aggressive histology
Intervention MeSH terms: Tositumomab I-131; Antibodies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a single-arm, open-label study of Iodine 131 Anti B1 Antibody for the treatment of
      1st or 2nd relapsed indolent B cell lymphomas or B cell lymphomas that have transformed to a
      more aggressive histology. The primary endpoint of the study is to determine the response
      rate. Secondary endpoints of the study is to determine the duration of response, time to
      progression, time-to-treatment failure, safety, and survival.

      Forty patients will receive therapy on this study at the 2 clinical sites. Patients will
      undergo 2 phases of the study. In the first phase, termed the "dosimetric dose", patients
      will receive an infusion of unlabeled Anti B1 Antibody (450 mg) over 70 minutes (including a
      10 minute flush) immediately followed by a 30 minute infusion (including a 10 minute flush)
      of Anti B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of Iodine 131. Whole body
      gamma camera scans will be obtained on 1) Day 0; 2) Day 2, 3, or 4; and 3) Day 6 or 7
      following the dosimetric dose. Using the dosimetric data from the 3 imaging timepoints, a
      patient-specific dose of Iodine 131 Anti B1 Antibody to deliver the desired total body dose
      of radiotherapy will be calculated. In the second phase, termed the "radioimmunotherapeutic
      dose", patients will receive a 70 minute infusion (including a 10 minute flush) of unlabeled
      Anti B1 Antibody (450 mg) immediately followed by a 30 minute infusion (including a 10 minute
      flush) of 35 mg Anti B1 Antibody labeled with the patient-specific dose of Iodine 131 to
      deliver a whole body dose of 75 cGy to patients with no hematologic risk factors. Patients
      who have platelet counts of 100,001-149,999 cells/mm3 will receive 65 cGy and patients who
      are obese will be dosed based upon 137% of their lean body mass (see Appendix A). Patients
      will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or
      potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine
      131 Anti B1 Antibody and continuing for 14 days following the last infusion of Iodine 131
      Anti B1 Antibody (i.e., therapeutic dose).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically-confirmed diagnosis of B-cell CLL/PLL/SLL;
             lymphoplasmacytic - immunocytoma; follicle center, follicular, grade I; or follicle
             center, follicular, grade II NHLs or one of these B-cell lymphomas which has
             transformed to a more aggressive histology (37).

          -  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 (>50% of tumor cells are positive) or evidence of CD20
             positivity by flow cytometry (>50% of tumor cells are positive) are acceptable
             evidence of CD20 positivity. Testing of tumor tissue from any time in the course of
             the patient's disease is acceptable.

          -  Patients must have received 1 or 2 prior chemotherapy regimens and have progressed
             following their last regimen. Patients who have received >2 prior chemotherapy
             regimens are excluded. Prior therapy with radiation, immunosuppressants, or steroids
             are not counted as chemotherapy regimens.

          -  Patients must have a performance status of at least 60% on the Karnofsky Scale (see
             Appendix B) and an anticipated survival of at least 3 months.

          -  Patients must have an absolute granulocyte count >1,500 x 109/l and a platelet count
             >100,000 x 109/l within 14 days of study entry. 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 upper
             limit of normal) and hepatic function (defined as total bilirubin <1.5 upper limit of
             normal and hepatic transaminases [AST + ALT] <5 x upper limit of normal) within 14
             days of study entry.

          -  Patients must have bi-dimensionally measurable disease. At least one lesion must be
             >/=2cm x 2 cm (by CT scan).

          -  Patients must be at least 18 years of age.

          -  Patients must give written informed consent and sign an EC-approved informed consent
             form prior to study entry.

        Exclusion Criteria:

          -  Patients 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 intratrabecular space involved exceeds 10% on a unilateral biopsy. The
             mean of bilateral biopsies must be no more than 25%. The procedure for bilateral bone
             marrow biopsy analysis of marrow involvement is included in Appendix C.

          -  Patients who have received cytotoxic chemotherapy, radiation therapy, or cytokine
             treatment within 4 weeks prior to study entry (6 weeks for nitrosourea compounds) or
             who exhibit persistent clinical evidence of toxicity. The use of systemic steroids
             must be discontinued one week prior to study entry.

          -  Patients with prior hematopoietic stem cell transplant following high-dose
             chemotherapy or chemo/radiotherapy.

          -  Patients with active obstructive hydronephrosis.

          -  Patients with evidence of active infection requiring IV antibiotics at the time of
             study entry.

          -  Patients with New York Heart Association class III or IV heart disease (see Appendix
             D) or other 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 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.

          -  Patients with known HIV infection.

          -  Patients with known brain or leptomeningeal metastases.

          -  Patients who are pregnant or breast-feeding. Patients of child-bearing potential must
             undergo a serum pregnancy test within 7 days prior to study entry and radiolabeled
             antibody is not to be administered until a negative result is obtained. Males and
             females must agree to use effective contraception for 6 months following treatment.

          -  Patients with previous allergic reactions to iodine. This does not include reacting to
             IV iodine-containing contrast materials.

          -  Patients who were previously given any monoclonal or polyclonal antibodies of any
             non-human species for either diagnostic or therapeutic purposes. This includes
             engineered chimeric and humanized antibodies.

          -  Patients who previously received radioimmunotherapy.

          -  Patients with progressive disease within 1 year of irradiation arising in a field that
             has been previously irradiated with >3500 cGy.

          -  Patients who are concurrently receiving either approved or non-approved (through
             another protocol) anti-cancer drugs or biologics.

          -  Patients who have received more than 2 prior chemotherapy regimens. Prior therapy with
             radiation, immunosuppressants, or steroids are not counted as chemotherapy regimens.