This phase I/II trial studies the side effects of giving reduced-intensity conditioning followed by donor peripheral blood stem cell transplant (PBSCT) and how well it works in treating patients with multiple myeloma (MM). Giving low doses of chemotherapy, such as fludarabine phosphate and melphalan, and total-body irradiation (TBI) before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after transplant may stop this from happening.
PRIMARY OBJECTIVES: I. To evaluate the efficacy of this approach by determining the 1-year progression-free survival (PFS) and overall survival (OS). II. To evaluate day 100 non-relapse mortality. III. To determine the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD. OUTLINE: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donors). After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months, and then annually thereafter for 5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Given IV
Given IV
Undergo TBI
Given PO
Given PO
Undergo reduced-intensity allogeneic PBSCT
Undergo reduced-intensity allogeneic PBSCT
Correlative studies
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
University of Torino
Torino, Italy
PFS
PFS will be calculated for all patients from the date of transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission. Progressive disease is defined as greater than 25% increase in serum or urine M proteins compared to best response status after autologous transplant and/or appearance of new lytic bone lesions or plasmocytomas.
Time frame: At 1 year post-transplant
Non-relapse Mortality
Early NRM will be monitored in a sequential fashion.
Time frame: At day 100
Incidence of Acute GVHD (Grades III-IV)
Number of patients with Grade III-IV acute GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.
Time frame: Up to 5 years
Incidence of Chronic (Extensive) GVHD
Number of subjects with chronic extensive GVHD post-transplant. Severe GVHD will be monitored in a sequential fashion.
Time frame: Up to 5 years
OS
Number of subjects surviving. OS will be estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
Time frame: At 6 months and then every year thereafter, up to 5 years
Engraftment
Number of subjects who engrafted post-transplant. Engraftment will be monitored in a sequential fashion.
Time frame: Up to 5 years
Relapse Rate
Number of subjects who relapsed after achieving CR post-transplant. Relapse rate will be summarized using cumulative incidence estimates.
Time frame: Up to 5 years
Response Rate
Number of subjects who achieved CR post-transplant. Response rate will be summarized using cumulative incidence estimates.
Time frame: Up to 5 years
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