Tandem Autologous HCT / Nonmyeloablative Allogeneic HCT From HLA-Matched Related and Unrelated Donors Followed by Bortezomib Maintenance Therapy for Patients With High-Risk Multiple Myeloma
I. Progression-free survival (PFS) at 2 years after the autograft (=< 50% in historic
I. Overall survival (OS) at 2 years after the autograft.
II. Non-relapse mortality (NRM) at 200 days and 1 year after allograft.
III. Incidence of grades II-IV acute graft-versus-host-disease (GVHD) and chronic extensive
IV. Safety of bortezomib maintenance therapy after stem cell transplantation.
PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Patients undergo PBSC mobilization and
collection using the preferred regimens at the participating institution.
CONDITIONING CHEMOTHERAPY AND AUTOLOGOUS OR SYNGENEIC HEMATOPOIETIC STEM CELL
TRANSPLANTATION (HSCT): Patients receive high-dose melphalan intravenously (IV) on day -2
followed by an autologous or syngeneic HSCT on day 0.
NON-MYELOABLATIVE ALLOGENEIC HSCT: Beginning 40-180 days after autologous HSCT, patients
receive 1 of the following regimens:
1. HLA-IDENTICAL RELATED DONOR: Patients receive cyclosporine IV or orally (PO) twice
daily (BID) starting on days -3 to 56, and taper until day 180. Patients then undergo
total-body irradiation (TBI) and non-myeloablative allogeneic HSCT on day 0. Four to
six hours after completion of allogeneic HSCT, patients receive mycophenolate mofetil
(MMF) PO BID on days 0-27.
2. HLA-UNRELATED DONOR: Patients receive fludarabine phosphate IV on days -4 to -2.
Patients also receive cyclosporine IV or PO BID starting on days -3 to 100 and taper
until day 180. Patients then undergo TBI and non-myeloablative allogeneic HSCT on day
0. Four to six hours after completion of allogeneic HSCT, patients receive MMF PO
thrice daily (TID) on days 0-27 and then BID on days 27-40 with taper of MMF on days
MAINTENANCE THERAPY: Beginning 60-120 days after allogeneic HSCT, patients receive
bortezomib subcutaneously (SC) on days 1 and 4 of 14-day cycles for 9 months or for up to 18
cycles in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 1 year and
then annually for up to 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Confidence intervals will be estimated.
At 2 years after the autograft
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|