This phase II trial studies the side-effects and anti-cancer effects of giving an autologous or syngeneic stem cell transplant followed by an allogeneic donor stem cell transplant and bortezomib. Patients treated on this trial have newly diagnosed high-risk, relapsed, or refractory multiple myeloma (MM). Giving chemotherapy before an autologous stem cell transplant slows or stops the growth of cancer cells by preventing them from dividing or killing them. Stem cells that were harvested earlier from the patient's blood and frozen are then returned to the patient to replace the blood-forming cells that were destroyed by chemotherapy. Giving chemotherapy and total-body irradiation before an allogeneic donor stem cell transplant also prevents the patient's immune system from rejecting the donor's stem cells. Undergoing an autologous or syngeneic stem cell transplantation followed by an allogeneic donor stem cell transplant and bortezomib may be overall more effective in killing cancer cells.
PRIMARY OBJECTIVES: I. Progression-free survival (PFS) at 2 years after the autograft (=\< 50% in historic controls). SECONDARY OBJECTIVES: 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 GVHD. IV. Safety of bortezomib maintenance therapy after stem cell transplantation. OUTLINE: 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 40-96. 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 treatment, patients are followed up every 3 months for 1 year and then annually for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Undergo transplantation
Given SC
Given IV
Given PO
Given IV
Correlative studies
Given IV
Given PO
Undergo transplantation
Undergo transplantation
Undergo transplantation
Undergo radiotherapy
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Patients Surviving Progression-free
Number of subjects surviving without progressive disease post-transplant. Progressive disease criteria: 1. Greater than 25% increase in serum (absolute increase must be ≥0.5 g/dL) or urine (absolute increase must be ≥200 mg/24h) M proteins compared to best response status after autologous transplant. 2. Appearance of new lytic bone lesions or plasmacytomas.
Time frame: At 2 years after the autograft
Number of Patients With Grade II-IV Acute GVHD
Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: 1. \- a maculopapular eruption involving \< 25% BSA 2. \- a maculopapular eruption involving 25 - 50% BSA 3. \- generalized erythroderma 4. \- generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. \- bilirubin 2.0 - 3.0 mg/100 mL 2. \- bilirubin 3 - 5.9 mg/100 mL 3. \- bilirubin 6 - 14.9 mg/100 mL 4. \- bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Time frame: 100 days post allo transplant
Number of Patients With Chronic GVHD
Number of subjects with classic chronic or chronic extensive GVHD post allogeneic transplant.
Time frame: 1 year post allo
Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy
Number of subjects with toxicities related to bortezomib maintenance therapy post-transplant.
Time frame: Up to 100 days after the autograft or allograft
Number of Patients With Non-relapse Mortality
Number of subjects with non-relapse mortalities post allogeneic transplant.
Time frame: 200 and 365 days after allo
Number of Patients Surviving Overall
Number of subjects surviving two years post autologous transplant.
Time frame: At 2 years after the autograft
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