NCT01009840 · REGISTRY CONDITION SEARCH

IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2026-05-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With Overall Disease Response at Month 6

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outcome · POSTED

Overall Survival

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outcome · POSTED

Percentage of Participants With Overall Survival Events

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Percentage of Participants With Progression-free Survival Events

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outcome · POSTED

Percent Change in IV Busulfan Dose

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outcome · POSTED

Ratio Area Under Curve (AUC)/Target AUC

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outcome · POSTED

Percent Difference Between Area Under Curve (AUC) and Target AUC

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outcome · POSTED

Percentage of Participants With Transplant-Related Mortality

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outcome · POSTED

Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: 1. Age 18 to 75 years, inclusive. 2. Subjects must have multiple myeloma which requires treatment for relapsed disease and are eligible for the planned autologous HSCT. 3. Subjects must have had one previous autologous HSCT, at least one year prior to the planned autologous HSCT in this study. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 5. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of child-bearing potential. 6. Subjects who are surgically sterile (ie, have undergone orchidectomy or hysterectomy); female subjects who have been postmenopausal for at least 12 consecutive months; or subjects who agree to remain abstinent or to practice double-barrier forms of birth control from trial screening through 30 days (for females) and 90 days (for males) from the last dose of the investigational medicinal product (IMP). If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control implant, condom, or sponge with spermicide. 7. Subjects in whom the minimum stem cell dose of 2.0 x 10\^6 cluster of differentiation 34 (CD34)+ cells/kg has been collected. 8. Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to comply with all requirements of the study. Exclusion Criteria: 1. Prior treatment history of allogeneic HSCT for any medical reason, not limited to myeloma treatment. 2. Prior treatment history of more than one autologous HSCT or high-dose chemotherapy with stem cell rescue for any medical reason, not limited to myeloma treatment. 3. Prior treatment with busulfan or gemtuzumab ozogamicin for any reason. 4. Presence of a t(4;14) or p53 gene deletion as determined by fluorescence in situ hybridization (FISH) during the screening process or documented t(4; 14) or p53 gene deletion obtained during a time of active disease by any method. 5. Systemic amyloidosis. 6. Known allergy to boron or any components of bortezomib. 7. Left ventricular ejection fraction (LVEF) \< 45% as measured by either multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) performed within 75 days prior to day of busulfan test dose. If cyclophosphamide was used for stem cell harvest, an ECHO or MUGA must be done prior to enrollment to confirm adequate cardiac function. 8. Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening. 9. Symptomatic pulmonary disease, based on Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) \< 50% of predicted (corrected for hemoglobin) measured within 75 days prior to day of busulfan test dose. 10. Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of normal (ULN), 11. History of elevated total serum bilirubin \>2 mg/dL that had been caused by previous chemotherapy at any point, or total bilirubin \> 2.0 mg/dL at the time of screening with the exception of Gilbert's disease. 12. Hepatic synthetic dysfunction evident International Normalized Ratio (INR) ≥ 2.0 at the time of screening. 13. Any previous history of fulminant liver failure, cirrhosis, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, and symptomatic biliary disease. 14. Prior total body irradiation therapy or radiation therapy directly applied to the liver. 15. Known history of or current hepatitis B, hepatitis C, HIV, or uncontrolled active infection of any kind at the time of test dose. If serology antibody studies are positive, a quantitative polymerase chain reaction (PCR) must be completed to confirm lack of active infection. 16. Serum creatinine \>2.0 mg/dL at the time of Screening. 17. ≥ Grade 1 neuropathy with pain, or \> Grade 2 neuropathy without pain (subjects with neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable without pain may be included). 18. Women who are pregnant or lactating. 19. Current or history of drug and/or alcohol abuse. 20. Use of other investigational therapies within 30 days
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: IV busulfan
Drug: bortezomib
Procedure: Autologous Hematopoietic Stem Cell Transplant (HSCT)
label
IV busulfan
type
EXPERIMENTAL

interventions

arm Group Labels
IV busulfan
description
PK-directed dosing of IV busulfan for 4 days
name
IV busulfan
other Names
Busulfex®
type
DRUG
arm Group Labels
IV busulfan
description
Single IV bortezomib at a dose of 1.3 mg/m\^2.
name
bortezomib
other Names
Velcade®
type
DRUG
arm Group Labels
IV busulfan
name
Autologous Hematopoietic Stem Cell Transplant (HSCT)
type
PROCEDURE

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 30
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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 \[Progressive Disease (PD)\].
measure
Percentage of Participants With Overall Disease Response at Month 6
time Frame
6 Months

secondary Outcomes

description
Esimated overall survival rate (percentage of participants) at Day 180
measure
Overall Survival
time Frame
6 Months
description
Overall Survival Event was death.
measure
Percentage of Participants With Overall Survival Events
time Frame
6 Months
description
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
measure
Progression-free Survival
time Frame
6 Months
description
Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.
measure
Percentage of Participants With Progression-free Survival Events
time Frame
6 Months
description
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.
measure
Percent Change in IV Busulfan Dose
time Frame
Baseline (Day -12 to -9), Day -5
description
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.
measure
Ratio Area Under Curve (AUC)/Target AUC
time Frame
Baseline (Day -12 to -9), Day -5
description
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.
measure
Percent Difference Between Area Under Curve (AUC) and Target AUC
time Frame
Baseline (Day -12 to -9), Day -5
description
The percentage of participants with death related to transplant.
measure
Percentage of Participants With Transplant-Related Mortality
time Frame
6 Months
description
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.
measure
Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria
time Frame
6 Months

Full study description

brief Summary: 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.
detailed Description: 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.

Source references