Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Condition: Blood Cancer; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Mixed chimerism transplantation is an approach to allogeneic transplants that attempts to
      decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish
      mixed chimerism using low dose total body irradiation along with immunosuppression using
      cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to
      allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host
      disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to
      convert the patient to a full chimera while developing a graft-vs-tumor effect.
    

Detailed description: 
      Participants are mobilized with cyclophosphamide 4 g/m2 and filgrastim 10 µg/kg/day for
      peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is
      high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue [ie, autologous
      hematopoietic cells transplant (auto-HCT)]. Post-infusion support includes filgrastim 5
      µg/kg/day, starting 6 days following melphalan. Participants with stable or responsive
      disease at 4 weeks eligible to continue on to the planned allogenic HCT (allo-HCT). For
      allo-HCT, a sibling donor that is fully matched for human leukocyte antigen (HLA-matched) is
      identified. Participants receive a single dose of total body irradiation (TBI) 200 centigray
      (cGy) as well as immunosuppression with cyclosporine (CSP) 6.25 mg/kg and mycophenolate
      mofetil (MMF) 15 mg/kg. The HLA-matched donor begins filgrastim injections 16 µg/kg/day on
      day -4 continuing to Day 0, with apheresis collections on Day -1 and Day 0, to a target of >
      5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication
      hydrocortisone 100 mg IV and diphenhydramine 50 mg IV. CSP will be tapered beginning Day 56
      with a goal of discontinuing CSP on Day 180, adjusted as needed.
    

Intervention name(s): Autologous hematopoietic cell transplant (Auto-HCT); Allogeneic hematopoietic cell transplant (Allo-HCT); Cyclophosphamide; Filgrastim; Melphalan; Total body irradiation (TBI); Cyclosporine (CSP); Mycophenolate Mofetil (MMF)
Intervention type(s): Procedure; Procedure; Drug; Drug; Drug; Radiation; Procedure; Drug
Intervention description(s): The target cell dose is 2.6 x 10e6 CD34+ cells/kg; The target cell dose is 5 x 10e6 CD34 cells/kg; Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion; Filgrastim 10 µg/kg/day to mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion (Auto-HCT)
Filgrastim 5 µg/kg/day starting 6 days after melphalan (Day 4 after Auto-HCT)
Filgrastim 16 µg/kg/day to mobilize donor peripheral blood progenitor cells (PBPC) for allogeneic transplant (Allo-HCT); Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT; 200 centigray (cGy) total body irradiation delivered on Day 0; Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56; Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27
Other intervention name(s): Cytoxan; Neosar; Neupogen; Granulocyte-colony stimulating factor (G-CSF); Melphalan hydrochloride; Melphalan HCl; Cyclosporine A; CellCept
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Melphalan; Cyclosporins; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment