90 Y-BC8-DOTA Monoclonal Antibody, Fludarabine Phosphate, and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma
Condition: Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and best dose of yttrium Y 90 anti-CD45
      monoclonal antibody BC8 when given together with fludarabine phosphate and total-body
      irradiation followed by donor peripheral blood stem cell transplant in treating patients with
      multiple myeloma. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45
      monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them
      without harming normal cells. Giving chemotherapy drugs, such as fludarabine phosphate, and
      total-body irradiation before a donor peripheral blood stem cell transplant helps stop the
      growth of cancer cells and helps stop the patient's immune system from rejecting the donor's
      stem cells. When the healthy stem cells from a donor are infused into the patient they may
      help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
      platelets. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells. Giving yttrium Y 90 anti-CD45 monoclonal antibody BC8, fludarabine
      phosphate, and total-body irradiation before the transplant together with cyclosporine and
      mycophenolate mofetil after the transplant may stop this from happening and may be an
      effective treatment for multiple myeloma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess the tissue localization of 111In-BC8-DOTA antibody therapy (Ab) and establish
      reproducibly favorable biodistribution.

      II. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-BC8-DOTA Ab
      when combined with fludarabine phosphate (FLU) and 2 Gy total-body irradiation (TBI) as a
      preparative regimen followed by human leukocyte antigen (HLA)-matched, related or unrelated
      hematopoietic cell transplant (HCT) for patients with multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To assess the potential efficacy of this approach, within the limits of a phase I study,
      by examining disease response, duration of remission, disease free survival (DFS), and
      overall survival (OS).

      OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8
      (90Y-BC8 Ab).

      Patients receive 90Y-BC8 Ab intravenously (IV) on day -12 and fludarabine phosphate IV on
      days -4 to -2. Patients undergo TBI and allogeneic peripheral blood stem cell transplant on
      day 0. Patients also receive graft-vs-host disease prophylaxis comprising cyclosporine orally
      (PO) twice daily (BID) on days -3 to 56 with taper to day 180 or on days -3 to 100 with taper
      to 180; and mycophenolate mofetil IV or PO BID on days 0-27, or 0-40 with taper to 96.

      After completion of study treatment, patients are followed up every 6 months for 2 years, and
      then annually thereafter.
    

Intervention name(s): Allogeneic Hematopoietic Stem Cell Transplantation; Cyclosporine; Fludarabine Phosphate; Mycophenolate Mofetil; Peripheral Blood Stem Cell Transplantation; Total-Body Irradiation; Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Intervention type(s): Procedure; Drug; Drug; Drug; Procedure; Radiation; Radiation
Intervention description(s): Undergo allogeneic peripheral blood stem cell transplantation; Given PO; Given IV; Given IV or PO; Undergo allogeneic peripheral blood stem cell transplantation; Undergo TBI; Given IV
Other intervention name(s): allogeneic stem cell transplantation; HSC; HSCT; 27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Gengraf; Neoral; OL 27-400; Sandimmun; Sandimmune; SangCya; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; Cellcept; MMF; PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; TOTAL BODY IRRADIATION; Whole-Body Irradiation; 90Y Anti-CD45 MoAb BC8
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Antibodies; Antibodies, Monoclonal; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment