Clinical trial NCT00899847
Conditions: Transplantation, Homologous Transplantation, Autologous Multiple Myeloma Blood and Marrow Transplant (BMT)
Sponsor: Stanford University
Start date: 2009-05-01; Completion date: 2014-12-01
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control. Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion. For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC. Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.
Interventions: intervention 1: Autologous peripheral blood stem cells (auto-PBSC) transplantation intervention 2: Allogeneic peripheral blood stem cells (allo-PBSC) transplantation intervention 3: Filgrastim intervention 4: Cyclophosphamide intervention 5: Melphalan intervention 6: Cyclosporine intervention 7: Total lymphoid irradiation intervention 8: Rabbit anti-thymocyte globulin intervention 9: Mycophenolate Mofetil 250mg intervention 10: Solumedrol intervention 11: Diphenhydramine intervention 12: Acetaminophen intervention 13: Hydrocortisone
Intervention descriptions: intervention 1: 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 intervention 2: Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy. intervention 3: 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. intervention 4: Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen. intervention 5: Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion. intervention 6: 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. intervention 7: 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. intervention 8: ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion. intervention 9: 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 intervention 10: Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion intervention 11: Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions. intervention 12: Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions. intervention 13: Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Protocol documents: