Trial Outcomes & Findings for Ph 2 Bortezomib, Dexamethasone, + Doxorubicin With ALCAR for Previously Treated Multiple Myeloma (NCT NCT00581919)
NCT ID: NCT00581919
Last Updated: 2019-12-13
Results Overview
Anti-tumor responses were analyzed descriptively and summarized in tabular format. Ninety percent confidence intervals for the percentage of subjects with a confirmed anti-tumor response were constructed using the method proposed by Duffy-Santner. Complete response defined as: no evidence of M-protein on immunofixation of serum and/or urine AND less than 5% plasma cells in the bone marrow biopsy. Partial response defined as: 50 to 99% decrease in M-protein on serum and/or urine protein electrophoresis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
Every 21 days, up to 24 weeks
Results posted on
2019-12-13
Participant Flow
Participants were recruited from University of Wisconsin Hospital and Clinics and the Wisconsin Oncology Network between April 2004 and September 2010.
No events between enrollment and group assignment. All subjects are enrolled are assigned to the same group.
Participant milestones
| Measure |
Bort, Dex, and Dox With ALCAR
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Overall Study
STARTED
|
32
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
24
|
Reasons for withdrawal
| Measure |
Bort, Dex, and Dox With ALCAR
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Death
|
1
|
|
Overall Study
Disease Progression
|
10
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Other Complicating Disease
|
1
|
|
Overall Study
Started Non-Protocol Therapy
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Ph 2 Bortezomib, Dexamethasone, + Doxorubicin With ALCAR for Previously Treated Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 Participants
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Age, Customized
30-39
|
1 participants
n=5 Participants
|
|
Age, Customized
40-49
|
4 participants
n=5 Participants
|
|
Age, Customized
50-59
|
6 participants
n=5 Participants
|
|
Age, Customized
60-69
|
12 participants
n=5 Participants
|
|
Age, Customized
70-79
|
7 participants
n=5 Participants
|
|
Age, Customized
80-89
|
2 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 21 days, up to 24 weeksAnti-tumor responses were analyzed descriptively and summarized in tabular format. Ninety percent confidence intervals for the percentage of subjects with a confirmed anti-tumor response were constructed using the method proposed by Duffy-Santner. Complete response defined as: no evidence of M-protein on immunofixation of serum and/or urine AND less than 5% plasma cells in the bone marrow biopsy. Partial response defined as: 50 to 99% decrease in M-protein on serum and/or urine protein electrophoresis.
Outcome measures
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 Participants
Bort, Dex, and Dox with ALCAR: Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bortezomib, Dexamethasone, Doxorubicin, and ALCAR
|
53 percentage of participants
Interval 36.0 to 69.0
|
SECONDARY outcome
Timeframe: From date of randomization until the date of death from any cause, assessed up to 7 yearsOutcome measures
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 Participants
Bort, Dex, and Dox with ALCAR: Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Overall Survival
|
28.3 months
Interval 0.2 to 75.3
|
SECONDARY outcome
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years.Progression is defined as any of the following: 1) 25% or greater increase in M-protein as measured by serum or urine protein electrophoresis. There must be an absolute minimum increase of 0.5 g/dl in serum M spike or 0.2 gram of specific urinary light chains to constitute progression, 2) 25% or greater increase in the percentage or plasma cells in the bone marrow biopsy, or 3) new bone lesions or an increase in the size of old lesions on x-ray.
Outcome measures
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 Participants
Bort, Dex, and Dox with ALCAR: Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Progression-free Survival
|
5 months
Interval 1.0 to 37.0
|
Adverse Events
Bort, Dex, and Dox With ALCAR
Serious events: 10 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 participants at risk
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Vascular disorders
Thrombosis/embolism - DVT
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
General disorders
Fever (in the absence of neutropenia)
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
CNS Hemorrhage/bleeding
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Hemorrhage - Other, specify: GI-esophagus
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Febrile neutropenia - pneumonia
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Infection with unknown ANC
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Infection without Neutropenia
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Infection/Febrile Neutropenia
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Infection/Febrile Neutropenia - Other, specify: Normal ANC, Gr 1 or 2 neutrophils
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness (not due to neuropathy)
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Neurology - Other, specify: encephalopathy
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Neurology - Other, specify: vocal cord paralysis
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Seizure
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.1%
1/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
Other adverse events
| Measure |
Bort, Dex, and Dox With ALCAR
n=32 participants at risk
Bortezomib 1.3 mg/m2 IV days 1, 4, 8, and 11 Dexamethasone 20 mg PO days 1, 4, 8, and 11 Doxorubicin 15 mg/m2 IV days 1 and 8 Acetyl-L-Carnitine (ALCAR) 1.5 g PO BID days 1-21 Maximum of 8 cycles. Each cycle is 21 days long
|
|---|---|
|
Gastrointestinal disorders
abdominal pain
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Alkaline phosphatase increased
|
18.8%
6/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Blood and lymphatic system disorders
Anemia
|
65.6%
21/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
8/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
back pain
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Bloating
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
21.9%
7/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Eye disorders
Blurred vision
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Injury, poisoning and procedural complications
Bruising
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Colitis
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Psychiatric disorders
Confusion
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Constipation
|
46.9%
15/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Creatine increased
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Dehydration
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Diarrhea
|
43.8%
14/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Dizziness
|
18.8%
6/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Dysphagia
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
General disorders
Edema limbs
|
28.1%
9/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Extrapyramidal involuntary movement
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
General disorders
Fatigue
|
53.1%
17/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
General disorders
Fever
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
21.9%
7/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Vascular disorders
Hypertension
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Vascular disorders
Hypotension
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Infections and infestations other, specify: with or without neutropenia
|
21.9%
7/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Psychiatric disorders
Insomnia
|
21.9%
7/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
LDH
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Lymphocyte count decrease
|
31.2%
10/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Metabolism and nutrition disorders
Metabolic changes
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder- other, specify: Joint pain
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
16/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Neuropathic pain
|
21.9%
7/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Neutrophil count decreased
|
46.9%
15/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Oral pain
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
4/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Peripheral motor neuropathy
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
68.8%
22/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Platelet count decreased
|
71.9%
23/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
18.8%
6/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Skin and subcutaneous tissue disorders
Sweating
|
9.4%
3/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Taste Alteration
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Infections and infestations
Upper respiratory infection
|
25.0%
8/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Renal and urinary disorders
Urinary frequency
|
6.2%
2/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Gastrointestinal disorders
Vomiting
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
Weight loss
|
15.6%
5/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
|
Investigations
White blood cell decreased
|
81.2%
26/32 • Adverse Events were collected while subjects were receiving study treatment through 30 days post last dose of study treatment, up to 28 weeks.
|
Additional Information
Dr. Natalie Callander
University of Wisconsin Hospital and Clinics
Phone: 608-265-8690
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place