Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
      ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and
      help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal
      antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry
      cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy,
      such as melphalan, work in different ways to stop the growth of cancer cells, either by
      killing the cells or by stopping them from dividing. A peripheral stem cell transplant using
      stem cells from the patient may be able to replace blood-forming cells that were destroyed by
      chemotherapy. Giving monoclonal antibody therapy together with chemotherapy and autologous
      peripheral stem cell transplant may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90
      ibritumomab tiuxetan when given together with rituximab, melphalan, and autologous peripheral
      stem cell transplant in treating patients with previously treated multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety of rituximab, yttrium Y 90 ibritumomab tiuxetan, high-dose
           melphalan, and autologous peripheral blood stem cell transplantation in patients with
           previously treated multiple myeloma.

        -  Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the
           clonotypic B-cells at baseline and at B-cell recovery in these patients.

      Secondary

        -  Determine the response rate and progression factors (time to progression,
           progression-free survival, and duration of response) in patients treated with this
           regimen.

        -  Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal
           plasma cells in the blood and marrow prior to high-dose melphalan.

      OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan.

      Patients receive rituximab IV followed by a dosimetry dose of indium In 111 ibritumomab
      tiuxetan IV over 10 minutes on day -22. Patients with acceptable biodistribution receive
      rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14,
      high-dose melphalan IV over 1 hour on days -2 and -1, and undergo autologous peripheral blood
      stem cell transplantation on day 0. Patients also receive sargramostim (GM-CSF)
      subcutaneously beginning on day 0 and continuing until blood counts recover.

      Cohorts of 3-6 patients receive escalating doses of yttrium Y 90 ibritumomab tiuxetan until
      the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that
      at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

      Bone marrow, blood, and urine samples are collected at baseline and then periodically during
      study for biomarker correlative studies.

      After completion of study treatment, patients are followed every 3 months for 5 years.
    

Intervention name(s): rituximab; melphalan; Stem Cell; Sargramostim (GM-CSF); 90Y-Zevalin; 111In Zevalin
Intervention type(s): Biological; Drug; Biological; Biological; Radiation; Biological
Intervention description(s): 375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22); 100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.; greater than or equal to 2 x 106 CD34+/kg by IV; 500 mcg by Subcutaneous QD; Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.; 5.0 mCi by IV
Other intervention name(s): Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigen; Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8
Intervention MeSH terms: Rituximab; Melphalan; Sargramostim; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I multiple myeloma; refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma