Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Condition: Blood Cancer; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Neoplasms
Intervention: 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 description: 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
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Melphalan; Cyclosporins; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        PATIENT INCLUSION CRITERIA

          -  Multiple myeloma, early Stage II-III or relapsed / progression after initial treatment
             of Stage I disease

          -  Patient has HLA-identical sibling donor

          -  Age ≤ 70 years

          -  No prior therapy which would preclude the use of low-dose total body irradiation

          -  Pathology review and diagnosis confirmation by Stanford University Medical Center

          -  Karnofsky performance status (KPS) > 70%

          -  DLCO ≥ 60% predicted

          -  ALT and AST < 2 x upper limit of normal (ULN)

          -  Total bilirubin < 2 mg/dL

          -  Serum creatinine < 2.0, or 24-hour creatinine clearance ≥ 60 mL/min

          -  HIV-negative

          -  Signed informed consent document

        PATIENT EXCLUSION CRITERIA

          -  Smoldering multiple myeloma; monoclonal gammopathy of unknown significance; or primary
             amyloidosis

          -  Severe psychological or medical illness

          -  Prior allogeneic hematopoietic cell transplantation

          -  Pregnant or lactating

        ALLOGENEIC DONOR INCLUSION CRITERIA

          -  Age ≥ 17

          -  HIV-seronegative

          -  Signed informed consent document

        ALLOGENEIC DONOR EXCLUSION CRITERIA

          -  Serious medical or psychological illness

          -  Pregnant or lactating

          -  Prior malignancies within the last 5 years, except for non-melanoma skin cancers