Study for the outcome and safety of individualized busulfan dosing with bortezomib for patients preparing for a second stem cell transplant to treat multiple myeloma.
Evaluation of six-month response in relapsed multiple myeloma subjects, who have had a prior autologous HSCT (greater than one year previously) receiving an IV busulfan-based conditioning regimen with the combination of pharmacokinetic (PK)-guided IV busulfan dosing and bortezomib, followed by a second autologous HSCT. Assessment of the safety profile of this conditioning regimen will also be completed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
PK-directed dosing of IV busulfan for 4 days
Single IV bortezomib at a dose of 1.3 mg/m\^2.
Arizona Cancer Center
Tucson, Arizona, United States
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States
Loyola University Medical Center
Percentage of Participants With Overall Disease Response at Month 6
The percentage of participants reported in each disease category by International Myeloma Working Group (IMWG) uniform response criteria for Multiple Myeloma 6 months after autologous Hematopoietic stem cell transplant. Overall Disease Response categories were: \[stringent Complete Response (sCR)=CR + normal Free Light Chain (FLC) ratio + absence of clonal cells in bone marrow\], \[Complete Response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow\], \[Very Good Partial Response (VGPR)=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein + urine M-protein level \<100 mg/24 hour\], \[Partial Response (PR)=≥50% reduction of serum M-protein and reduction in 24 hour urine M-protein by ≥90% or to \<200 mg per 24 hour\], \[Stable Disease (SD)=Not meeting criteria for CR, VGPR, PR or progressive disease\] or \[Progressive Disease (PD)\].
Time frame: 6 Months
Overall Survival
Esimated overall survival rate (percentage of participants) at Day 180
Time frame: 6 Months
Percentage of Participants With Overall Survival Events
Overall Survival Event was death.
Time frame: 6 Months
Progression-free Survival
Progression-free Survival (PFS) defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease (PD) by IMWG criteria. PD was defined as an Increase of ≥25% from the lowest response value in any one or more of the following: 1)Serum M-component and/or (the absolute increase must be ≥0.5 g/dL), 2)Urine M-component and/or (the absolute increase must be ≥200 mg/24 hr), 3)In patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL, 4)Bone marrow plasma cell percentage; the absolute percentage must be ≥10%, 5)Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas and/or 6)Development of hypercalcaemia that can be attributed solely to the plasma cell proliferative diso
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Maywood, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
University of Maryland School of Medicine - Marlene & Stewart Greenebaum Cancer Center
Baltimore, Maryland, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
University of Pennsylvania -Abramson Cancer Center
Philadelphia, Pennsylvania, United States
The Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States
South Texas Veterans Health Care System
San Antonio, Texas, United States
Texas Transplant Physician Group, PLLC
San Antonio, Texas, United States
...and 3 more locations
Time frame: 6 Months
Percentage of Participants With Progression-free Survival Events
Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.
Time frame: 6 Months
Percent Change in IV Busulfan Dose
The percent change in dose is relative to the busulfan dose administered at the Baseline Visit (Day -12 to -9) when a dose of 0.8 mg/kg was administered and on Day -5 when the Seattle Cancer Care Alliance recommended PK-adjusted dose was administered.
Time frame: Baseline (Day -12 to -9), Day -5
Ratio Area Under Curve (AUC)/Target AUC
A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. Gas chromatography with mass selective detection (GC-MS) was used to determine the busulfan level in plasma. The ratio was calculated: AUC/Target AUC.
Time frame: Baseline (Day -12 to -9), Day -5
Percent Difference Between Area Under Curve (AUC) and Target AUC
A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. GC-MS was used to determine the busulfan level in plasma. The percent difference was calculated between AUC and the Target AUC.
Time frame: Baseline (Day -12 to -9), Day -5
Percentage of Participants With Transplant-Related Mortality
The percentage of participants with death related to transplant.
Time frame: 6 Months
Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria
The Baltimore criteria for veno-occlusive disease was defined as the development of hyperbilirubinemia with serum bilirubin \> 2 mg/dl within 21 days after transplantation and at least 2 of the following clinical signs and symptoms: (1) hepatomegaly, usually painful, (2) \> 5% weight gain, or (3) ascites.
Time frame: 6 Months