Trial Outcomes & Findings for Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma (NCT NCT00784823)
NCT ID: NCT00784823
Last Updated: 2022-08-11
Results Overview
The Maximum Tolerated Dose of Bortezomib (MTD) Will be Defined as the Dose Level Prior to That Resulting in Two Out of Six Patients Experiencing a DLT
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
32 participants
Primary outcome timeframe
During dosing of Bortezomib on Day -4 to Day -1 of ASCT
Results posted on
2022-08-11
Participant Flow
Participant milestones
| Measure |
Phase I Cohort - Bortezomib Dose 1 mg/m2
Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase I Cohort - Bortezomib 1.3 mg/m2
Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase I Cohort - Bortezomib 1.6 mg/m2
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase II Cohort
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
3
|
20
|
|
Overall Study
COMPLETED
|
6
|
3
|
3
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Phase I Cohort - Bortezomib Dose 1 mg/m2
n=6 Participants
Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase I Cohort - Bortezomib 1.3 mg/m2
n=3 Participants
Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase I Cohort - Bortezomib 1.6 mg/m2
n=3 Participants
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase II Cohort
n=20 Participants
Bortezomib 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
57 years
n=6 Participants
|
63 years
n=3 Participants
|
58 years
n=3 Participants
|
57 years
n=20 Participants
|
57 years
n=32 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=6 Participants
|
2 Participants
n=3 Participants
|
1 Participants
n=3 Participants
|
9 Participants
n=20 Participants
|
17 Participants
n=32 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=6 Participants
|
1 Participants
n=3 Participants
|
2 Participants
n=3 Participants
|
11 Participants
n=20 Participants
|
15 Participants
n=32 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
6 participants
n=6 Participants
|
3 participants
n=3 Participants
|
3 participants
n=3 Participants
|
20 participants
n=20 Participants
|
32 participants
n=32 Participants
|
PRIMARY outcome
Timeframe: During dosing of Bortezomib on Day -4 to Day -1 of ASCTThe Maximum Tolerated Dose of Bortezomib (MTD) Will be Defined as the Dose Level Prior to That Resulting in Two Out of Six Patients Experiencing a DLT
Outcome measures
| Measure |
Combined Dose Intense Melphalan With Bortezomib (MTD)
n=32 Participants
The purpose of this study is to determine the tolerance and potential efficacy of combining dose intense melphalan with escalating doses of bortezomib in patients with multiple myeloma undergoing autologous stem cell transplantation.
Combined dose intense Melphalan with maximum tolerated dose of bortezomib (MTD)
Bortezomib: - Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line
* Bortezomib will be administered any time on day -4 and 24 hrs after the start of the melphalan infusion on day -1
* Dosing will be based on actual body weight Patient weight must be measured within seven days of the start of the treatment regimen
Melphalan: - Melphalan is administered by rapid intravenous infusion via a central or peripheral vein over one hour
* Melphalan will be dissolved with 10 ml of diluent to a concentration of 5 mg/mL which is then immediately diluted in 0.9% normal saline to a concentration NOT exceeding 0.45 mg/mL prior to administration
* The final dilution of melphalan is physically and chemically stable for 60 minutes and therefore will be administered within that time period
* Melphalan will be given as a single dose (not split over 2 or more days)
* Dosing will be based body surface area calculated using actual body weight
|
|---|---|
|
The Maximum Tolerated Dose of Bortezomib (MTD)
|
1.6 mg/m2 of bortezomib
|
Adverse Events
Phase I Cohort
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Phase II Cohort
Serious events: 6 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I Cohort
n=12 participants at risk
Bortezomib was dose escalated at 1, 1.3, and 1.6 mg/m2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase II Cohort
n=20 participants at risk
Bortezomib 1.6 mg/m2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
|---|---|---|
|
General disorders
Death
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Seizure
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Respiratory, thoracic and mediastinal disorders
ICU Admission For Respiratory Distress
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Blood and lymphatic system disorders
Engraftment Syndrome
|
16.7%
2/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Immune system disorders
Guillain-Barre Syndrome
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolus
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
Other adverse events
| Measure |
Phase I Cohort
n=12 participants at risk
Bortezomib was dose escalated at 1, 1.3, and 1.6 mg/m2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
Phase II Cohort
n=20 participants at risk
Bortezomib 1.6 mg/m2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Shorness of Breath
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
20.0%
4/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Musculoskeletal and connective tissue disorders
Humerus Fracture
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
C. diff
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Gram-positive bacteremia
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
15.0%
3/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Gram-negative bacteremia
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Polymicrobial sepsis
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Herpes Zoster
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Candida Bacteremia
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Renal and urinary disorders
Tumor Lysis Syndrome
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Aspiration Pneumonia
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Fever
|
25.0%
3/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Infections and infestations
Neutropenic Fever
|
25.0%
3/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
25.0%
5/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Cardiac disorders
Hypotension
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Cardiac disorders
Hypertension
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Nausea
|
41.7%
5/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
30.0%
6/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Anorexia
|
33.3%
4/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
15.0%
3/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Mucositis
|
33.3%
4/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
20.0%
4/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Esophagitis
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Gastrointestinal disorders
Pancreatic Enzyme Elevations
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Neuropathy
|
25.0%
3/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Seizures
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Fatigue
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Syncope
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Nervous system disorders
Altered Mental Status
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
5.0%
1/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Renal and urinary disorders
Renal Impairment
|
0.00%
0/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
10.0%
2/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
|
Renal and urinary disorders
Hypokalemia
|
8.3%
1/12
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
0.00%
0/20
The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place