A Phase 2 interventional study of IV busulfan and bortezomib in Multiple Myeloma, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 13 sites in 2 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-13.
Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. · Phase 2, Interventional, and Treatment
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.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 30 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
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Exclusion Criteria:
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m\^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.
Drug: IV busulfan · Drug: bortezomib · Procedure: Autologous Hematopoietic Stem Cell Transplant (HSCT)
PK-directed dosing of IV busulfan for 4 days
Also known as: Busulfex®
Single IV bortezomib at a dose of 1.3 mg/m\^2.
Also known as: Velcade®
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
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
| Milestone | IV Busulfan |
|---|---|
| Started | 30 |
| Completed | 16 |
| Not completed | 14 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Adverse event | 4 |
| Withdrew: Subject met withdrawal criteria | 7 |
| Withdrew: Subject was withdrawn by investigator | 1 |
| Withdrew: Subject withdrew consent to participate | 1 |
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 \[Progressive Disease (PD)\].
| Percentage of participants | IV Busulfan |
|---|---|
| sCR or CR or VGPR | 20.0 |
| PR or SD or PD | 70.0 |
| Not Assessed | 10.0 |
Esimated overall survival rate (percentage of participants) at Day 180
| percentage of participants | IV Busulfan |
|---|---|
| Overall Survival | 85.9 |
Overall Survival Event was death.
| Percentage of participants | IV Busulfan |
|---|---|
| Percentage of Participants With Overall Survival Events | 13.3 |
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
| Days | IV Busulfan |
|---|---|
| Progression-free Survival | 191 (92 to NA) |
Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.
| Percentage of participants | IV Busulfan |
|---|---|
| Percentage of Participants With Progression-free Survival Events | 50.0 |
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.
| Percent change | IV Busulfan |
|---|---|
| Percent Change in IV Busulfan Dose | 7.55 (-26.00 to 47.50) |
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.
| Ratio | IV Busulfan |
|---|---|
| Ratio Area Under Curve (AUC)/Target AUC | 1.00 (0.89 to 1.19) |
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.
| Percent difference | IV Busulfan |
|---|---|
| Percent Difference Between Area Under Curve (AUC) and Target AUC | -0.22 (-10.97 to 18.55) |
The percentage of participants with death related to transplant.
| Percentage of participants | IV Busulfan |
|---|---|
| Percentage of Participants With Transplant-Related Mortality | 3.3 |
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.
| Percentage of participants | IV Busulfan |
|---|---|
| Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria | 0.0 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IV Busulfan | — | 18/30 (60%) | 30/30 (100%) |
| Event | IV Busulfan |
|---|---|
| StomatitisGastrointestinal disorders | 5/30 |
| PyrexiaGeneral disorders | 3/30 |
| NauseaGastrointestinal disorders | 2/30 |
| VomitingGastrointestinal disorders | 2/30 |
| Renal failure acuteRenal and urinary disorders | 2/30 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/30 |
| DiarrhoeaGastrointestinal disorders | 1/30 |
| Multi-organ failureGeneral disorders | 1/30 |
| Bacterial sepsisInfections and infestations | 1/30 |
| Bronchitis bacterialInfections and infestations | 1/30 |
| Event | IV Busulfan |
|---|---|
| StomatitisGastrointestinal disorders | 28/30 |
| DiarrhoeaGastrointestinal disorders | 26/30 |
| NauseaGastrointestinal disorders | 24/30 |
| FatigueGeneral disorders | 20/30 |
| Febrile neutropeniaBlood and lymphatic system disorders | 17/30 |
| Decreased appetiteMetabolism and nutrition disorders | 17/30 |
| HypokalaemiaMetabolism and nutrition disorders | 15/30 |
| ConstipationGastrointestinal disorders | 13/30 |
| VomitingGastrointestinal disorders | 13/30 |
| PyrexiaGeneral disorders | 13/30 |
| Age, Continuous(years) | IV Busulfan |
|---|---|
| Mean | 59.1 ± 6.9 |
| Sex/Gender, Customized(Participants) | IV Busulfan |
|---|---|
| Female | 5 |
| Male | 25 |
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Otsuka Pharmaceutical Development & Commercialization, Inc.