Trial Outcomes & Findings for IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients (NCT NCT01009840)

NCT ID: NCT01009840

Last Updated: 2026-05-13

Results Overview

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 \[Progressive Disease (PD)\].

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

6 Months

Results posted on

2026-05-13

Participant Flow

Participant milestones

Participant milestones
Measure
IV Busulfan
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the pharmacokinetic (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 hematopoietic stem cell transplant (HSCT).
Overall Study
STARTED
30
Overall Study
COMPLETED
16
Overall Study
NOT COMPLETED
14

Reasons for withdrawal

Reasons for withdrawal
Measure
IV Busulfan
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the pharmacokinetic (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 hematopoietic stem cell transplant (HSCT).
Overall Study
Lost to Follow-up
1
Overall Study
Adverse Event
4
Overall Study
Subject Met Withdrawal Criteria
7
Overall Study
Subject was Withdrawn by Investigator
1
Overall Study
Subject Withdrew Consent to Participate
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
IV Busulfan
n=30 Participants
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.
Age, Continuous
59.1 years
STANDARD_DEVIATION 6.9 • n=1512 Participants
Sex/Gender, Customized
Female
5 Participants
n=1512 Participants
Sex/Gender, Customized
Male
25 Participants
n=1512 Participants

PRIMARY outcome

Timeframe: 6 Months

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

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 \[Progressive Disease (PD)\].

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percentage of Participants With Overall Disease Response at Month 6
sCR or CR or VGPR
20.0 Percentage of participants
Percentage of Participants With Overall Disease Response at Month 6
PR or SD or PD
70.0 Percentage of participants
Percentage of Participants With Overall Disease Response at Month 6
Not Assessed
10.0 Percentage of participants

SECONDARY outcome

Timeframe: 6 Months

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

Esimated overall survival rate (percentage of participants) at Day 180

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Overall Survival
85.9 percentage of participants

SECONDARY outcome

Timeframe: 6 Months

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

Overall Survival Event was death.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percentage of Participants With Overall Survival Events
13.3 Percentage of participants

SECONDARY outcome

Timeframe: 6 Months

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

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

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Progression-free Survival
191 Days
Interval 92.0 to
The upper limit of the 95% CI could not be estimated. Follow-up was restricted to 6 months post transplant.

SECONDARY outcome

Timeframe: 6 Months

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percentage of Participants With Progression-free Survival Events
50.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day -12 to -9), Day -5

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

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.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percent Change in IV Busulfan Dose
7.55 Percent change
Interval -26.0 to 47.5

SECONDARY outcome

Timeframe: Baseline (Day -12 to -9), Day -5

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

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.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Ratio Area Under Curve (AUC)/Target AUC
1.00 Ratio
Interval 0.89 to 1.19

SECONDARY outcome

Timeframe: Baseline (Day -12 to -9), Day -5

Population: Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

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.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percent Difference Between Area Under Curve (AUC) and Target AUC
-0.22 Percent difference
Interval -10.97 to 18.55

SECONDARY outcome

Timeframe: 6 Months

Population: Safety population included all participants who received IV busulfan.

The percentage of participants with death related to transplant.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percentage of Participants With Transplant-Related Mortality
3.3 Percentage of participants

SECONDARY outcome

Timeframe: 6 Months

Population: Safety population included all participants who received IV busulfan.

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.

Outcome measures

Outcome measures
Measure
IV Busulfan
n=30 Participants
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.
Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria
0.0 Percentage of participants

Adverse Events

IV Busulfan

Serious events: 18 serious events
Other events: 30 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
IV Busulfan
n=30 participants at risk
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.
Renal and urinary disorders
Renal failure acute
6.7%
2/30
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
3.3%
1/30
Respiratory, thoracic and mediastinal disorders
Dyspnoea
3.3%
1/30
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
3.3%
1/30
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicity
3.3%
1/30
Skin and subcutaneous tissue disorders
Dermatitis
3.3%
1/30
Vascular disorders
Deep vein thrombosis
3.3%
1/30
Vascular disorders
Venoocclusive disease
3.3%
1/30
Blood and lymphatic system disorders
Febrile neutropenia
3.3%
1/30
Gastrointestinal disorders
Diarrhoea
3.3%
1/30
Gastrointestinal disorders
Nausea
6.7%
2/30
Gastrointestinal disorders
Stomatitis
16.7%
5/30
Gastrointestinal disorders
Vomiting
6.7%
2/30
General disorders
Multi-organ failure
3.3%
1/30
General disorders
Pyrexia
10.0%
3/30
Infections and infestations
Bacterial sepsis
3.3%
1/30
Infections and infestations
Bronchitis bacterial
3.3%
1/30
Infections and infestations
Device related infection
3.3%
1/30
Infections and infestations
Septic shock
3.3%
1/30
Infections and infestations
Tinea versicolour
3.3%
1/30
Infections and infestations
Viral infection
3.3%
1/30
Nervous system disorders
Cranial neuropathy
3.3%
1/30
Nervous system disorders
Headache
3.3%
1/30
Renal and urinary disorders
Renal failure
3.3%
1/30

Other adverse events

Other adverse events
Measure
IV Busulfan
n=30 participants at risk
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.
Blood and lymphatic system disorders
Anaemia
6.7%
2/30
Blood and lymphatic system disorders
Febrile neutropenia
56.7%
17/30
Blood and lymphatic system disorders
Neutropenia
6.7%
2/30
Blood and lymphatic system disorders
Thrombocytopenia
6.7%
2/30
Cardiac disorders
Palpitations
13.3%
4/30
Cardiac disorders
Sinus tachycardia
6.7%
2/30
Cardiac disorders
Tachycardia
16.7%
5/30
Eye disorders
Dry eye
6.7%
2/30
Eye disorders
Vision blurred
10.0%
3/30
Gastrointestinal disorders
Abdominal discomfort
6.7%
2/30
Gastrointestinal disorders
Abdominal distension
6.7%
2/30
Gastrointestinal disorders
Abdominal pain
13.3%
4/30
Gastrointestinal disorders
Anal inflammation
6.7%
2/30
Gastrointestinal disorders
Constipation
43.3%
13/30
Gastrointestinal disorders
Diarrhoea
86.7%
26/30
Gastrointestinal disorders
Dry mouth
13.3%
4/30
Gastrointestinal disorders
Dyspepsia
6.7%
2/30
Gastrointestinal disorders
Dysphagia
20.0%
6/30
Gastrointestinal disorders
Flatulence
10.0%
3/30
Gastrointestinal disorders
Gastrooesophageal reflux disease
10.0%
3/30
Gastrointestinal disorders
Hematochezia
10.0%
3/30
Gastrointestinal disorders
Haemorrhoids
10.0%
3/30
Gastrointestinal disorders
Nausea
80.0%
24/30
Gastrointestinal disorders
Odynophagia
6.7%
2/30
Gastrointestinal disorders
Oesophagitis
6.7%
2/30
Gastrointestinal disorders
Oral pain
10.0%
3/30
Gastrointestinal disorders
Stomatitis
93.3%
28/30
Gastrointestinal disorders
Vomiting
43.3%
13/30
General disorders
Asthenia
16.7%
5/30
General disorders
Chest pain
10.0%
3/30
General disorders
Chills
23.3%
7/30
General disorders
Fatigue
66.7%
20/30
General disorders
Oedema
10.0%
3/30
General disorders
Oedema peripheral
33.3%
10/30
General disorders
Pyrexia
43.3%
13/30
Infections and infestations
Bacterial infection
6.7%
2/30
Infections and infestations
Bronchitis
6.7%
2/30
Infections and infestations
Candidiasis
6.7%
2/30
Infections and infestations
Clostridial infection
6.7%
2/30
Infections and infestations
Device related infection
6.7%
2/30
Infections and infestations
Pneumonia
13.3%
4/30
Infections and infestations
Sepsis
6.7%
2/30
Injury, poisoning and procedural complications
Contusion
6.7%
2/30
Injury, poisoning and procedural complications
Excoriation
6.7%
2/30
Injury, poisoning and procedural complications
Skin laceration
10.0%
3/30
Investigations
Alanine aminotransferase increased
10.0%
3/30
Investigations
Aspartate aminotransferase increased
13.3%
4/30
Investigations
Blood calcium decreased
6.7%
2/30
Investigations
Blood creatinine increased
13.3%
4/30
Investigations
Blood glucose increased
6.7%
2/30
Investigations
Blood lactate dehydrogenase increased
10.0%
3/30
Investigations
Blood potassium decreased
6.7%
2/30
Investigations
International normalised ratio increased
6.7%
2/30
Investigations
Neutrophil count decreased
6.7%
2/30
Investigations
Weight decreased
26.7%
8/30
Investigations
White blood cell count decreased
6.7%
2/30
Metabolism and nutrition disorders
Decreased appetite
56.7%
17/30
Metabolism and nutrition disorders
Dehydration
13.3%
4/30
Metabolism and nutrition disorders
Hyperglycaemia
20.0%
6/30
Metabolism and nutrition disorders
Hyperphosphataemia
10.0%
3/30
Metabolism and nutrition disorders
Hypoalbuminaemia
13.3%
4/30
Metabolism and nutrition disorders
Hypocalcaemia
13.3%
4/30
Metabolism and nutrition disorders
Hypokalaemia
50.0%
15/30
Metabolism and nutrition disorders
Hypomagnesaemia
20.0%
6/30
Metabolism and nutrition disorders
Hyponatraemia
10.0%
3/30
Metabolism and nutrition disorders
Hypophosphataemia
20.0%
6/30
Metabolism and nutrition disorders
Malnutrition
6.7%
2/30
Musculoskeletal and connective tissue disorders
Arthralgia
26.7%
8/30
Musculoskeletal and connective tissue disorders
Back pain
6.7%
2/30
Musculoskeletal and connective tissue disorders
Bone pain
13.3%
4/30
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
6.7%
2/30
Musculoskeletal and connective tissue disorders
Neck pain
6.7%
2/30
Musculoskeletal and connective tissue disorders
Pain in extremity
20.0%
6/30
Musculoskeletal and connective tissue disorders
Pain in jaw
6.7%
2/30
Nervous system disorders
Dizziness
30.0%
9/30
Nervous system disorders
Dysgeusia
30.0%
9/30
Nervous system disorders
Headache
30.0%
9/30
Nervous system disorders
Memory impairment
6.7%
2/30
Nervous system disorders
Neuropathy peripheral
20.0%
6/30
Nervous system disorders
Peripheral sensory neuropathy
6.7%
2/30
Nervous system disorders
Sinus headache
6.7%
2/30
Nervous system disorders
Somnolence
6.7%
2/30
Psychiatric disorders
Anxiety
16.7%
5/30
Psychiatric disorders
Confusional state
10.0%
3/30
Psychiatric disorders
Depression
10.0%
3/30
Psychiatric disorders
Hallucination
13.3%
4/30
Psychiatric disorders
Insomnia
23.3%
7/30
Renal and urinary disorders
Dysuria
13.3%
4/30
Renal and urinary disorders
Haematuria
6.7%
2/30
Renal and urinary disorders
Renal failure
10.0%
3/30
Renal and urinary disorders
Renal failure acute
10.0%
3/30
Renal and urinary disorders
Urinary retention
6.7%
2/30
Reproductive system and breast disorders
Scrotal erythema
6.7%
2/30
Respiratory, thoracic and mediastinal disorders
Cough
36.7%
11/30
Respiratory, thoracic and mediastinal disorders
Dysphonia
10.0%
3/30
Respiratory, thoracic and mediastinal disorders
Dyspnoea
20.0%
6/30
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
16.7%
5/30
Respiratory, thoracic and mediastinal disorders
Epistaxis
16.7%
5/30
Respiratory, thoracic and mediastinal disorders
Hiccups
10.0%
3/30
Respiratory, thoracic and mediastinal disorders
Hypoxia
13.3%
4/30
Respiratory, thoracic and mediastinal disorders
Lung infiltration
10.0%
3/30
Respiratory, thoracic and mediastinal disorders
Nasal congestion
13.3%
4/30
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
33.3%
10/30
Respiratory, thoracic and mediastinal disorders
Pharyngeal inflammation
13.3%
4/30
Respiratory, thoracic and mediastinal disorders
Pleural effusion
6.7%
2/30
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
10.0%
3/30
Respiratory, thoracic and mediastinal disorders
Sinus congestion
6.7%
2/30
Skin and subcutaneous tissue disorders
Alopecia
20.0%
6/30
Skin and subcutaneous tissue disorders
Dermatitis
6.7%
2/30
Skin and subcutaneous tissue disorders
Dry skin
20.0%
6/30
Skin and subcutaneous tissue disorders
Erythema
13.3%
4/30
Skin and subcutaneous tissue disorders
Petechiae
6.7%
2/30
Skin and subcutaneous tissue disorders
Pruritus
13.3%
4/30
Skin and subcutaneous tissue disorders
Rash
26.7%
8/30
Skin and subcutaneous tissue disorders
Skin disorder
10.0%
3/30
Skin and subcutaneous tissue disorders
Skin exfoliation
6.7%
2/30
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
20.0%
6/30
Vascular disorders
Flushing
13.3%
4/30
Vascular disorders
Hypertension
13.3%
4/30
Vascular disorders
Hypotension
23.3%
7/30

Additional Information

clinical Transparency

Otsuka

Phone: 1-800-441-6763

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place