Radiolabeled Monoclonal Antibody Therapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Lymphoma or Waldenstrom's Macroglobulinemia
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Waldenstrom Macroglobulinemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver
      cancer-killing substances to them without harming normal cells. Peripheral stem cell
      transplantation may be able to replace immune cells that were destroyed by monoclonal
      antibody therapy used to kill cancer cells.

      PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody
      therapy plus peripheral stem cell transplantation in treating patients who have lymphoma or
      Waldenstrom's macroglobulinemia that has not responded to previous therapy.
    

Detailed description: 
      OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of
      radioimmunotherapy using high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2
      (Y90 MOAB hLL2) followed by autologous peripheral blood stem cell transplantation in patients
      with B cell lymphomas or Waldenstrom's macroglobulinemia. II. Determine the organ and tumor
      dosimetry for comparison to clinical measurement of toxicity and antitumor responses in these
      patients. III. Determine magnitude and duration of human anti-humanized LL2 antibody (HAhLL2)
      or anti-DOTA response in these patients. IV. Evaluate the extent and duration of antitumor
      response to this regimen in these patients.

      OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to
      prior treatment (high dose chemotherapy with transplantation vs low dose chemotherapy with
      radioimmunotherapy (RAIT) vs low dose chemotherapy without RAIT). Patients receive filgrastim
      (G-CSF) subcutaneously (SC) daily for 5 days and undergo harvest of peripheral blood stem
      cells (PBSC). If an adequate number of CD34+ cells are not harvested, autologous bone marrow
      may be used. Patients undergo pretherapy imaging with indium In 111 monoclonal antibody MN-14
      (In111-MN-14) IV on day -7. If at least 1 tumor site is targeted, patients receive high dose
      yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2) IV for up to 50
      minutes on day 0. PBSC or bone marrow is reinfused approximately 7-14 days following infusion
      of Y90 MOAB hLL2. Patients also receive G-CSF SC daily until 3 days after blood counts have
      recovered. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB hLL2 until the
      maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
      which 2 of 6 patients experience dose limiting toxicity. Patients are followed weekly for 2
      months, monthly for 6 months, and then every 6 months for 5 years.

      PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 2 years.
    

Intervention name(s): filgrastim; autologous bone marrow transplantation; peripheral blood stem cell transplantation; indium In 111 monoclonal antibody MN-14; yttrium Y 90 epratuzumab
Intervention type(s): Biological; Procedure; Procedure; Radiation; Radiation
Intervention description(s): as prescribed by physician; 1-2 weeks before treatment; 1-2 weeks before treatment; intravenous infusion over 30 min; single dose; intravenous infusion over 30 min; single dose
Intervention MeSH terms: Epratuzumab; Antibodies; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Waldenstrom macroglobulinemia; recurrent adult acute lymphoblastic leukemia; refractory chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia; B-cell adult acute lymphoblastic leukemia; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma