Multiple MyelomaPhase 2NCT01009840
IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients
A Phase 2 study testing IV busulfan, bortezomib and Autologous Hematopoietic Stem Cell Transplant (HSCT) in people with Multiple Myeloma, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 13 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- IV busulfan, bortezomib and Autologous Hematopoietic Stem Cell Transplant (HSCT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 1 May 2010to 1 Mar 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 75 years, inclusive.
- Subjects must have multiple myeloma which requires treatment for relapsed disease and are eligible for the planned autologous HSCT.
- Subjects must have had one previous autologous HSCT, at least one year prior to the planned autologous HSCT in this study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of child-bearing potential.
- 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.
- Subjects in whom the minimum stem cell dose of 2.0 x 10^6 cluster of differentiation 34 (CD34)+ cells/kg has been collected.
- 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.
Who cannot join
- Prior treatment history of allogeneic HSCT for any medical reason, not limited to myeloma treatment.
- 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.
- Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.
- 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.
- Systemic amyloidosis.
- Known allergy to boron or any components of bortezomib.
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- 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.
- Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening.
- 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.
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of normal (ULN),
- 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.
- Hepatic synthetic dysfunction evident International Normalized Ratio (INR) ≥ 2.0 at the time of screening.
- 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.
- Prior total body irradiation therapy or radiation therapy directly applied to the liver.
- 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.
- Serum creatinine >2.0 mg/dL at the time of Screening.
- ≥ 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).
- Women who are pregnant or lactating.
- Current or history of drug and/or alcohol abuse.
- Use of other investigational therapies within 30 days
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States11 sites
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
University of Maryland School of Medicine - Marlene & Stewart Greenebaum Cancer Center
Baltimore, Maryland, 21201
Karmanos Cancer Institute
Detroit, Michigan, 48201
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Loyola University Medical Center
Maywood, Illinois, 60153
University of Pennsylvania -Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
The Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
South Texas Veterans Health Care System
San Antonio, Texas, 78229
Texas Transplant Physician Group, PLLC
San Antonio, Texas, 78229
Arizona Cancer Center
Tucson, Arizona, 85724
Canada2 sites
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 2a Study of Once Daily Intravenous Busulfan With Bortezomib, Followed by an Autologous Hematopoietic Stem Cell Transplant (HSCT) in Subjects With Relapsed Multiple Myeloma After Prior Autologous HSCT
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- IV busulfan, bortezomib, Autologous Hematopoietic Stem Cell Transplant (HSCT)
- Keywords
- Multiple Myeloma, Bone marrow transplant, Stem cell transplant, Busulfan, Bortezomib
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV busulfanDrug
Also called Busulfex®
PK-directed dosing of IV busulfan for 4 days
bortezomibDrug
Also called Velcade®
Single IV bortezomib at a dose of 1.3 mg/m^2.
Autologous Hematopoietic Stem Cell Transplant (HSCT)Procedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| IV busulfan | Experimental | 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. Receives: Drug: IV busulfan; Drug: bortezomib; Procedure: Autologous Hematopoietic Stem Cell Transplant (HSCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)].
Measured: 6 Months
Secondary outcomes (9)
Overall Survival
Esimated overall survival rate (percentage of participants) at Day 180
Measured: 6 Months
Percentage of Participants With Overall Survival Events
Overall Survival Event was death.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day -12 to -9), Day -5
Percentage of Participants With Transplant-Related Mortality
The percentage of participants with death related to transplant.
Measured: 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.
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study start1 May 2010
- Primary completion1 Mar 2012
- Study completion1 Mar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009840
- Sponsor's protocol ID
- 273-08-205
- Status last verified
- Apr 2026
- First submitted
- 6 Nov 2009
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Study of Once Daily Intravenous Busulfan With Bortezomib, Followed by an Autologous Hematopoietic Stem Cell Transplant (HSCT) in Subjects With Relapsed Multiple Myeloma After Prior Autologous HSCT
- ClinicalTrials.gov ID
- NCT01009840
- Acronym / sponsor ID
- 273-08-205
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Bone marrow transplant, Stem cell transplant, Busulfan, Bortezomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 May 2010 (actual)
- Primary completion
- 1 Mar 2012 (actual)
- Study completion
- 1 Mar 2012 (actual)
- First posted
- 9 Nov 2009 (estimated)
- Results
- Posted 7 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IV busulfan | Experimental | Drug: IV busulfan, Drug: bortezomib, Procedure: Autologous Hematopoietic Stem Cell Transplant (HSCT)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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 75 years, inclusive.
- Subjects must have multiple myeloma which requires treatment for relapsed disease and are eligible for the planned autologous HSCT.
- Subjects must have had one previous autologous HSCT, at least one year prior to the planned autologous HSCT in this study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of child-bearing potential.
Key exclusion criteria (20 listed)
- Prior treatment history of allogeneic HSCT for any medical reason, not limited to myeloma treatment.
- 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.
- Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.
- 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.
- Systemic amyloidosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV busulfanAlso: Busulfex®PK-directed dosing of IV busulfan for 4 days | Drug | IV busulfan |
| bortezomibAlso: Velcade®Single IV bortezomib at a dose of 1.3 mg/m^2. | Drug | IV busulfan |
| Autologous Hematopoietic Stem Cell Transplant (HSCT) | Procedure or surgery | IV busulfan |
Primary outcome
Percentage of Participants With Overall Disease Response at Month 6
Time frame: 6 Months
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)].
9 secondary outcomes
Overall Survival
Time frame: 6 Months
Percentage of Participants With Overall Survival Events
Time frame: 6 Months
Progression-free Survival
Time frame: 6 Months
Percentage of Participants With Progression-free Survival Events
Time frame: 6 Months
Percent Change in IV Busulfan Dose
Time frame: Baseline (Day -12 to -9), Day -5
Ratio Area Under Curve (AUC)/Target AUC
Time frame: Baseline (Day -12 to -9), Day -5
Percent Difference Between Area Under Curve (AUC) and Target AUC
Time frame: Baseline (Day -12 to -9), Day -5
Percentage of Participants With Transplant-Related Mortality
Time frame: 6 Months
Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria
Time frame: 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Otsuka Clinical Trial WebsiteLink provided by the sponsor.
- Otsuka Clinical Trial TransparencyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV busulfan, bortezomib and Autologous Hematopoietic Stem Cell Transplant (HSCT) in people with Multiple Myeloma, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Overall Disease Response at Month 6 (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026; AzTrials last refreshed its copy on 26 Oct 2026.