Trial Outcomes & Findings for Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis (NCT NCT01078454)
NCT ID: NCT01078454
Last Updated: 2022-02-01
Results Overview
sCR: ACR and no clonal cells in bone marrow (BM) ACR: Negative serum/urine immunofixation (IF), \<5% plasma cells in BM, and normal serum FLC ratio VGPR: 1. PR and any of the following; 2. serum/urine M-protein detectable by IF but not measurable (NM) on electrophoresis (EP); (3) ≥90% reduction in serum M-component and urine M-protein \<100 mg/24 hr if baseline serum measurable; (4) urine M-component \<100 mg/24 hr and NM serum M-protein on serum protein EP if baseline urine measurable; (5) ≥90% drop in the difference between involved and uninvolved FLC levels if only FLC measurable PR: (1) ≥50% drop of serum M-protein and 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline serum/urine measurable; or (2) ≥50% drop of serum M-protein if only serum measurable at baseline; or (3) 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline urine measurable; or (4) ≥ 50% drop in the difference between involved and uninvolved FLC if only FLC measu
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
11 participants
Primary outcome timeframe
Assessed at 3 months
Results posted on
2022-02-01
Participant Flow
Participants were recruited from ECOG member institutions between November 1, 2010 and September 7, 2012.
Participant milestones
| Measure |
Arm A (Mel-Dex)
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
5
|
|
Overall Study
COMPLETED
|
5
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Arm A (Mel-Dex)
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis
Baseline characteristics by cohort
| Measure |
Arm A (Mel-Dex)
n=6 Participants
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
n=5 Participants
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68 years
n=93 Participants
|
66 years
n=4 Participants
|
67 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Assessed at 3 monthsPopulation: All enrolled patients are included in this analysis.
sCR: ACR and no clonal cells in bone marrow (BM) ACR: Negative serum/urine immunofixation (IF), \<5% plasma cells in BM, and normal serum FLC ratio VGPR: 1. PR and any of the following; 2. serum/urine M-protein detectable by IF but not measurable (NM) on electrophoresis (EP); (3) ≥90% reduction in serum M-component and urine M-protein \<100 mg/24 hr if baseline serum measurable; (4) urine M-component \<100 mg/24 hr and NM serum M-protein on serum protein EP if baseline urine measurable; (5) ≥90% drop in the difference between involved and uninvolved FLC levels if only FLC measurable PR: (1) ≥50% drop of serum M-protein and 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline serum/urine measurable; or (2) ≥50% drop of serum M-protein if only serum measurable at baseline; or (3) 24-hr urinary M-protein drop by ≥90% or to \<200 mg/24 hr if baseline urine measurable; or (4) ≥ 50% drop in the difference between involved and uninvolved FLC if only FLC measu
Outcome measures
| Measure |
Arm A (Mel-Dex)
n=6 Participants
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
n=5 Participants
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Proportion of Patients With Hematologic Overall Response (Partial Response [PR]+ Very Good PR [VGPR]+ Amyloid Complete Response [ACR]+ Stringent Complete Response [sCR]) After 3 Months (3 Cycles) of Therapy
|
0.33 Proportion of patients
Interval 0.06 to 0.73
|
0.60 Proportion of patients
Interval 0.19 to 0.92
|
Adverse Events
Arm A (Mel-Dex)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Arm B (B-Mel-Dex)
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A (Mel-Dex)
n=6 participants at risk
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
n=5 participants at risk
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
General disorders
Fatigue
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
Other adverse events
| Measure |
Arm A (Mel-Dex)
n=6 participants at risk
Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Arm B (B-Mel-Dex)
n=5 participants at risk
Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m\^2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fatigue
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
40.0%
2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
40.0%
2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Lung infection
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
40.0%
2/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
1/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Thromboembolic event
|
16.7%
1/6 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/5 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
Additional Information
Study Statistician
ECOG Statistical Office
Phone: 617-632-3012
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60