Clinical Trial of Consolidation Treatment With Iodine I 131 Tositumomab for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Iodine I 131 Tositumomab
Intervention description: The Bexxar therapeutic regimen is delivered in two sets of intravenous infusions given 7-14 days apart. Nonradioactive Tositumomab is given before both the "dosimetric" infusion and the "therapeutic" infusion to improve distribution of these doses throughout the body. A trace amount of radioactive Iodine 131 attached to Tositumomab is initially given to enable physicians to evaluate the clearance of radiation from your body with gamma camera scans. Calculations made on the basis of these individualized radiation clearance rates allow the therapeutic dose (given 7-14 days after the dosimetric infusion) to be tailored for each patient. The therapeutic dose contains Tositumomab labeled with the amount of Iodine 131 tositumomab specifically calculated for you based on the scans performed following the dosimetric dose.
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: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is for patients with newly diagnosed or relapsed multiple myeloma. The main
      purpose of this study is to see how their disease responds to consolidation treatment
      (treatment aimed at further decreasing cancer cells) with a radioactive antibody (protein)
      called iodine I 131 tositumomab (known by the tradename Bexxar®) and also to look at the side
      effects which occur with this type of treatment. The investigators will also be looking at
      how long disease responds to treatment, if it responds at all, and how long patients who have
      had this treatment survive.

      Bexxar is a monoclonal antibody (protein) to which radioactive iodine 131 is attached. The
      monoclonal antibody in Bexxar (tositumomab), targets a protein called CD20 found on the
      surface of a variety of B-cells, including lymphoma cells, and some myeloma cells. The
      antibody is given as an infusion and finds its way to these cells. The radioactive iodine
      attached to the antibody delivers radiation directly to these cells which works to harm or
      kill the cancer cells. Approximately 20-25% of patients with multiple myeloma have this
      protein on the surface of their tumor cells. In addition, this protein was found on the
      surface of myeloma stem cells. While myeloma stem cells represent a minority of all myeloma
      cells (less than 5%), these cells are resistant to chemotherapy and are believed to be
      responsible for a recurrence of the disease after chemotherapy. In this study, Bexxar will be
      used after patients complete a course of chemotherapy and have residual myeloma cells left in
      their body. The Investigators are hoping that the treatment with Bexxar will decrease and
      possibly eliminate residual myeloma cells resistant to chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Expected survival ≥ 6 months

          -  Pre-study performance status of 0, 1, or 2 according to the World Health Organization
             (WHO)

          -  Newly diagnosed or relapsed/refractory myeloma with histologic confirmation of
             multiple myeloma by the Department of Pathology at University of Michigan Cancer
             Center (UMCC)

          -  Not more than 3 lines of therapy for myeloma for patients with relapsed disease

          -  Documented Stage II or III multiple myeloma (Durie and Salmon, 1975) prior to
             initiation of first line therapy

          -  At least 4 cycles of first line (for newly diagnosed patients) or salvage (for
             relapsed/refractory patients) prior therapy and in a plateau of at least partial
             response (Blade et al, 1999) for at least 2 determinations 6 weeks apart

          -  At least 21 days from day 1 of the last cycle and fully recovered from all toxicities
             associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy

          -  Measurable M-proteins with greater than 1 g/dl serum monoclonal protein and/or greater
             than 0.5 g/24 hour urine light chain excretion

          -  Acceptable hematologic status within two weeks prior to patient registration,
             including:

               -  Absolute neutrophil count ([segmented neutrophils + bands] x total white blood
                  cell [WBC]) ≥ 1,500/mm3;

               -  Platelet counts ≥ 150,000/mm3; these patients will receive total body dose of 75
                  cGy of Bexxar; or

               -  Platelet counts from 100,000/mm3 to 149,000/mm3; these patients will receive a 65
                  cGy total body dose of Bexxar;

               -  In patients previously treated with ASCT, total body dose will be 55 cGy in
                  patients with platelet count > 150,000 and 45 cGy in patients with platelets
                  100,000-149,000.

          -  Female patients who are not pregnant or lactating

          -  Men and women of reproductive potential who are following accepted birth control
             methods (as determined by the treating physician)

          -  Patients previously on Phase II drugs if no long-term toxicity is expected, and the
             patient has been off the drug for three or more weeks with no significant post
             treatment toxicities observed

          -  Patients determined to have < 25% bone marrow involvement with myeloma within six
             weeks of registration (based on bilateral core biopsy).

        Exclusion Criteria:

          -  Patients with impaired bone marrow reserve, as indicated by one or more of the
             following:

               -  Platelet count < 100,000 cells/mm3;

               -  Hypocellular bone marrow;

               -  Marked reduction in bone marrow precursors of one or more cell lines
                  (granulocytic, megakaryocytic, erythroid);

               -  History of failed stem cell collection;

               -  Myelodysplastic syndrome (MDS) or evidence of other than myeloma clonogenic
                  abnormalities;

               -  Prior radioimmunotherapy;

               -  Prior anti-CD20 therapy;

               -  Other than myeloma malignancy, except B-cell non-Hodgkin's lymphoma, basal and
                  squamous cell carcinoma of the skin, and cervical and breast cancer in situ,
                  unless patient is cancer free for > 3 years;

               -  Central nervous system (CNS) involvement;

               -  Patients with known HIV infection;

               -  Patients with pleural effusion;

               -  Patients with abnormal liver function: total bilirubin > 2.0 mg/dL;

               -  Patients with abnormal renal function: serum creatinine > 2.0 mg/dL;

               -  Patients who have received prior external beam radiation therapy to > 25% of
                  active bone marrow (involved field or regional);

               -  Patients who have received G-CSF or GM-CSF therapy within two weeks prior to
                  treatment;

               -  Serious nonmalignant disease or infection which, in the opinion of the
                  investigator and/or the sponsor, would compromise other protocol objectives;

               -  Major surgery, other than diagnostic surgery, within four weeks;

               -  Presence of anti-murine antibody (HAMA) reactivity. This result must be available
                  prior to receiving treatment for those patients with prior exposure to murine
                  antibodies or proteins.