Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG
Condition: Transplantation, Homologous; Transplantation, Autologous; Multiple Myeloma; Blood and Marrow Transplant (BMT)
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant
      approach for patients with advanced stage multiple myeloma.
    

Detailed description: 
      Development of cell-based immunotherapy from allogeneic hematopoietic cell transplantation
      (HCT) is dependent upon stable T-cell engraftment and the success of this therapeutic
      approach is likely to be greatest when directed against a minimal rather than gross tumor
      burden. To this end, tandem transplants with high dose therapy and autologous hematopoietic
      cell transplantation (AHCT) for tumor cytoreduction followed by non-myeloablative
      allotransplant have been conducted. In myeloma, this tandem approach results in greater
      efficacy compared to conventional AHCT.
    

Intervention name(s): Autologous peripheral blood stem cells (auto-PBSC) transplantation; Allogeneic peripheral blood stem cells (allo-PBSC) transplantation; Filgrastim; Cyclophosphamide; Melphalan; Cyclosporine; Total lymphoid irradiation; Rabbit anti-thymocyte globulin; Mycophenolate Mofetil 250mg; Solumedrol; Diphenhydramine; Acetaminophen; Hydrocortisone
Intervention type(s): Procedure; Procedure; Drug; Drug; Drug; Drug; Radiation; Biological; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Auto-PBSC ≥ 2 to 3 x 10e6 CD34+ cells/kg are intravenously (IV) infused as part of the combination stem cell therapy.
and allogeneic stem cells are administered intravenous (IV) infusion to reestablish hematopoietic function in patients whose bone marrow or immune system is damaged or defective; Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.; Filgrastim is administered subcutaneously (SC) at 10 µg/kg/day for auto-PBSC mobilization starting day 2 of mobilization until the last day of apheresis.
Filgrastim is administered SC at 5 µg/kg/day from Day 6 after auto-PBSC infusion to hematologic recovery.
Filgrastim is administered SC at 16 µg/kg/day for donor allo-PBSC mobilization at from Day - 4 to Day 0, prior to allo-PBSC collection.; Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.; Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.; Cyclosporine is administered by mouth (PO) for allo-PBSC graft vs host disease (GvHD) prophylaxis at 5 mg/kg from Day -3 through Bay +56. Tacrolimus may substituted.; Total lymphoid irradiation is administered at 80 centigrey (cGy) on Day -11 to -7; and Day -4 to -2 before alllo-PBSC infusion. TLI is also administered at 80 centigrey (cGy) x 2 on Day -1 before alllo-PBSC infusion.; ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.; MMF is administered at 15 mg/kg 3x/day by mouth (PO) after allo-PBSC through Day 40, followed by 10% dose reduction weekly (dose taper) through day 96, and adjusted if there is evidence of MMF-related GI toxicity or excessive myelosuppression; Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion; Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.; Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.; Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.
Other intervention name(s): auto-PBPC; Autologous peripheral blood progenitor cells (auto-PBPC) transplantation; allo-PBSC; Allogeneic peripheral blood progenitor cells (allo-PBPC) transplantation; Neupogen; Granulocyte colony-stimulating factor (G-CSF); r-metHuG-CSF; Ciclofosfamida; Ciclofosfamide; Claphene; CP monohydrate (CPM); CSP; L-Sarcolysin; L-phenylalanine mustard (L-PAM); L-Sarcolysin phenylalanine mustard; L-sarcolysine; Cyclosporin; Cyclosporin A; Ciclosporin; CSP; TLI; Thymoglobulin; ATG; CellCept; MMF; Solumedin; Soludecadron; Benadryl; Tylenol
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Cyclosporine; Mycophenolic Acid; Hydrocortisone; Methylprednisolone Hemisuccinate; Cyclophosphamide; Melphalan; Mechlorethamine; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment