Clinical trial NCT00185614
Conditions: Blood Cancer Multiple Myeloma
Sponsor: Wen-Kai Weng
Start date: 2000-08-01; Completion date: 2010-04-01
Enrollment: 63 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: Auto-HCT mobilization is cyclophosphamide 4 g/m2 + 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 is filgrastim 5 µg/kg/day, starting 6 days after melphalan. Stable/responsive disease at 4 weeks continues to allogenic HCT (Allo-HCT) from sibling donor fully-matched for human leukocyte antigen (HLA). Allo-HCT conditioning is total body irradiation (TBI) 200 centigray (cGy) + cyclosporine (CSP) 6.25 mg/kg + mycophenolate mofetil (MMF) 15 mg/kg. Donor mobilization is filgrastim 16 µg/kg/day on day -4 to Day 0; apheresis collections on Day -1 \& 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 \& diphenhydramine 50 mg IV. CSP tapering on Day 56 to Day 180, adjusted as needed.
Interventions: intervention 1: Autologous hematopoietic cell transplant (Auto-HCT) intervention 2: Allogeneic hematopoietic cell transplant (Allo-HCT) intervention 3: Cyclophosphamide intervention 4: Filgrastim intervention 5: Melphalan intervention 6: Total body irradiation (TBI) intervention 7: Cyclosporine (CSP) intervention 8: Mycophenolate Mofetil (MMF)
Intervention descriptions: intervention 1: The target cell dose is 2.6 x 10e6 CD34+ cells/kg intervention 2: The target cell dose is 5 x 10e6 CD34 cells/kg intervention 3: Cyclophosphamide administered intravenously (IV) at 4 mg /m² mobilize peripheral blood progenitor cells (PBPC) for autologous re-infusion intervention 4: * 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) intervention 5: Melphalan 200 mg/m2 (high-dose) intravenously as conditioning for Auto-HCT intervention 6: 200 centigray (cGy) total body irradiation delivered on Day 0 intervention 7: Cyclosporine administered twice-daily by mouth at a dose of 6.25 mg/kg from Day -3 through Day 56 intervention 8: Mycophenolate mofetil will begin at 15 mg/kg twice-daily by mouth from Day 0 to Day 27

Protocol documents: