Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma
Condition: Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects of giving reduced-intensity conditioning
      followed by donor peripheral blood stem cell transplant (PBSCT) and how well it works in
      treating patients with multiple myeloma (MM). Giving low doses of chemotherapy, such as
      fludarabine phosphate and melphalan, and total-body irradiation (TBI) before a donor PBSCT
      helps stop the growth of cancer cells. It may also stop the patient's immune system from
      rejecting the donor's stem cells. The donated stem cells may replace the patient's immune
      cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the
      transplanted cells from a donor can also make an immune response against the body's normal
      cells. Giving mycophenolate mofetil and cyclosporine after transplant may stop this from
      happening.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of this approach by determining the 1-year progression-free
      survival (PFS) and overall survival (OS).

      II. To evaluate day 100 non-relapse mortality.

      III. To determine the incidences of grades II-IV acute graft-versus-host disease (GVHD) and
      chronic extensive GVHD.

      OUTLINE:

      PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30
      minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2.
      Patients also undergo low-dose TBI on day 0.

      TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

      IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to
      80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180
      (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related
      donors) or thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donors).

      After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months,
      and then annually thereafter for 5 years.
    

Intervention name(s): fludarabine phosphate; melphalan; total-body irradiation; mycophenolate mofetil; cyclosporine; nonmyeloablative allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; laboratory biomarker analysis
Intervention type(s): Drug; Drug; Radiation; Drug; Drug; Procedure; Procedure; Other
Intervention description(s): Given IV; Given IV; Undergo TBI; Given PO; Given PO; Undergo reduced-intensity allogeneic PBSCT; Undergo reduced-intensity allogeneic PBSCT; Correlative studies
Other intervention name(s): 2-F-ara-AMP; Beneflur; Fludara; Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; TBI; Cellcept; MMF; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Melphalan; Cyclosporins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment