Trial Outcomes & Findings for Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study (NCT NCT00793650)
NCT ID: NCT00793650
Last Updated: 2012-08-30
Results Overview
Peripheral blood progenitor cells were collected with either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10\^6/kg CD34+ cells (range, 2.3-65) as their transplant graft.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
39 participants
Primary outcome timeframe
Day 30 after transplant
Results posted on
2012-08-30
Participant Flow
Participant milestones
| Measure |
Bortezomib Before HD Melphalan
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
20
|
|
Overall Study
COMPLETED
|
19
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study
Baseline characteristics by cohort
| Measure |
Bortezomib Before HD Melphalan
n=19 Participants
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
n=20 Participants
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Age Continuous
|
58.32 years
STANDARD_DEVIATION 7.92 • n=93 Participants
|
58.75 years
STANDARD_DEVIATION 8.05 • n=4 Participants
|
58.54 years
STANDARD_DEVIATION 7.88 • n=27 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=93 Participants
|
20 participants
n=4 Participants
|
39 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Day 30 after transplantPopulation: As per the protocol
Peripheral blood progenitor cells were collected with either chemo-mobilization (27 of 39, 69%) or growth factor mobilization (12 of 39, 31%). Patients received an average of 9.0 × 10\^6/kg CD34+ cells (range, 2.3-65) as their transplant graft.
Outcome measures
| Measure |
Bortezomib Before HD Melphalan
n=19 Participants
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
n=20 Participants
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
|---|---|---|
|
Safety and Engraftment
Median time for platelet recovery
|
16 days
Interval 8.0 to 23.0
|
16 days
Interval 10.0 to 58.0
|
|
Safety and Engraftment
Median time for neutrophil recovery
|
12 days
Interval 10.0 to 18.0
|
12 days
Interval 9.0 to 35.0
|
SECONDARY outcome
Timeframe: 100 days after transplantPopulation: As per the protocol.
CR :Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24 hour. Partial Response:\>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200mg per 24 hour.
Outcome measures
| Measure |
Bortezomib Before HD Melphalan
n=19 Participants
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
n=20 Participants
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
|---|---|---|
|
Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant.
Complete response (CR)
|
2 participants
|
6 participants
|
|
Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant.
VGPR-Very good partial remission
|
9 participants
|
11 participants
|
|
Response Rate Using EBMT(European Group for Blood and Bone Marrow Transplan) Criteria at Day +100 After Transplant.
Partial Response
|
6 participants
|
7 participants
|
Adverse Events
Bortezomib Before HD Melphalan
Serious events: 4 serious events
Other events: 19 other events
Deaths: 0 deaths
Bortezomib After HD melphalanAll
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bortezomib Before HD Melphalan
n=19 participants at risk
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
n=20 participants at risk
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
|---|---|---|
|
General disorders
Expired
|
15.8%
3/19
|
5.0%
1/20
|
|
General disorders
Acute pulmonary embolus
|
0.00%
0/19
|
5.0%
1/20
|
|
General disorders
Hemorrhage/Bleeding-Hemorrhage
|
5.3%
1/19
|
0.00%
0/20
|
Other adverse events
| Measure |
Bortezomib Before HD Melphalan
n=19 participants at risk
All patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours before administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
Bortezomib After HD melphalanAll
n=20 participants at risk
patients received melphalan (100 mg/m\^2/day × 2; days
-3 and -2), for a total dose of 200 mg/m\^2. Patients were randomized to receive bortezomib 24 hours after administration of high-dose melphalan in escalating dose cohorts of 1.0, 1.3, and 1.6 mg/m\^2
|
|---|---|---|
|
Gastrointestinal disorders
Muscositis
|
94.7%
18/19
|
80.0%
16/20
|
|
Gastrointestinal disorders
Diarrhea
|
84.2%
16/19
|
90.0%
18/20
|
|
Gastrointestinal disorders
Nausea
|
100.0%
19/19
|
90.0%
18/20
|
|
Gastrointestinal disorders
Vomiting
|
57.9%
11/19
|
55.0%
11/20
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
57.9%
11/19
|
65.0%
13/20
|
|
Infections and infestations
Sepsis
|
15.8%
3/19
|
10.0%
2/20
|
|
Hepatobiliary disorders
Liver Toxicities
|
26.3%
5/19
|
20.0%
4/20
|
|
Gastrointestinal disorders
Clostridium diificile
|
15.8%
3/19
|
5.0%
1/20
|
|
Renal and urinary disorders
Renal toxicities
|
21.1%
4/19
|
35.0%
7/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.5%
2/19
|
25.0%
5/20
|
|
Nervous system disorders
Cognitive disturbances
|
10.5%
2/19
|
5.0%
1/20
|
|
Nervous system disorders
Seizures
|
5.3%
1/19
|
0.00%
0/20
|
|
Vascular disorders
DVT/PE
|
5.3%
1/19
|
5.0%
1/20
|
|
Gastrointestinal disorders
Esophagitis
|
5.3%
1/19
|
0.00%
0/20
|
|
General disorders
Hypernatremia
|
10.5%
2/19
|
5.0%
1/20
|
|
General disorders
Headaches
|
5.3%
1/19
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/19
|
5.0%
1/20
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicities
|
10.5%
2/19
|
25.0%
5/20
|
|
Renal and urinary disorders
Incontinenece
|
5.3%
1/19
|
0.00%
0/20
|
|
Gastrointestinal disorders
Gastrointestinal bleed
|
5.3%
1/19
|
0.00%
0/20
|
|
Gastrointestinal disorders
Neutopenic colitis
|
0.00%
0/19
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Blisters on Feet
|
5.3%
1/19
|
0.00%
0/20
|
|
Renal and urinary disorders
Urinary retension
|
0.00%
0/19
|
5.0%
1/20
|
|
Cardiac disorders
Hypotension
|
21.1%
4/19
|
10.0%
2/20
|
|
Cardiac disorders
A.fib
|
5.3%
1/19
|
0.00%
0/20
|
|
Cardiac disorders
sinus bradycardia
|
5.3%
1/19
|
0.00%
0/20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place