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Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis

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ClinicalTrials.gov Identifier: NCT01078454
Recruitment Status : Completed
First Posted : March 2, 2010
Results First Posted : November 26, 2014
Last Update Posted : November 26, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Light Chain Deposition Disease
Primary Systemic Amyloidosis
Interventions Drug: melphalan
Drug: dexamethasone
Drug: bortezomib
Enrollment 11
Recruitment Details Participants were recruited from ECOG member institutions between November 1, 2010 and September 7, 2012.
Pre-assignment Details  
Arm/Group Title Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 6 5
Completed 5 3
Not Completed 1 2
Reason Not Completed
Adverse Event             1             1
Death             0             1
Arm/Group Title Arm A (Mel-Dex) Arm B (B-Mel-Dex) Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 6 5 11
Hide Baseline Analysis Population Description
All enrolled patients are included in this analysis.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 5 participants 11 participants
68
(61 to 78)
66
(44 to 72)
67
(44 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
Female
3
  50.0%
2
  40.0%
5
  45.5%
Male
3
  50.0%
3
  60.0%
6
  54.5%
1.Primary Outcome
Title 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
Hide Description 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
Time Frame Assessed at 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled patients are included in this analysis.
Arm/Group Title Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 6 5
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Proportion of patients
0.33
(0.06 to 0.73)
0.60
(0.19 to 0.92)
Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/6 (16.67%)   3/5 (60.00%) 
General disorders     
Fatigue  1  1/6 (16.67%)  0/5 (0.00%) 
Investigations     
Neutrophil count decreased  1  1/6 (16.67%)  0/5 (0.00%) 
Platelet count decreased  1  1/6 (16.67%)  1/5 (20.00%) 
White blood cell decreased  1  1/6 (16.67%)  0/5 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  1/6 (16.67%)  0/5 (0.00%) 
Dehydration  1  1/6 (16.67%)  0/5 (0.00%) 
Hypocalcemia  1  0/6 (0.00%)  1/5 (20.00%) 
Hypokalemia  1  1/6 (16.67%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness  1  1/6 (16.67%)  1/5 (20.00%) 
Vascular disorders     
Hypotension  1  1/6 (16.67%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A (Mel-Dex) Arm B (B-Mel-Dex)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/6 (16.67%)   5/5 (100.00%) 
Blood and lymphatic system disorders     
Anemia  1  1/6 (16.67%)  1/5 (20.00%) 
Gastrointestinal disorders     
Constipation  1  0/6 (0.00%)  1/5 (20.00%) 
Diarrhea  1  0/6 (0.00%)  1/5 (20.00%) 
Dyspepsia  1  1/6 (16.67%)  0/5 (0.00%) 
Nausea  1  1/6 (16.67%)  2/5 (40.00%) 
Vomiting  1  1/6 (16.67%)  0/5 (0.00%) 
General disorders     
Fatigue  1  1/6 (16.67%)  2/5 (40.00%) 
Infections and infestations     
Lung infection  1  0/6 (0.00%)  1/5 (20.00%) 
Urinary tract infection  1  1/6 (16.67%)  0/5 (0.00%) 
Investigations     
Platelet count decreased  1  0/6 (0.00%)  1/5 (20.00%) 
White blood cell decreased  1  1/6 (16.67%)  0/5 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  1/6 (16.67%)  1/5 (20.00%) 
Hyperglycemia  1  0/6 (0.00%)  1/5 (20.00%) 
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness  1  0/6 (0.00%)  2/5 (40.00%) 
Nervous system disorders     
Dizziness  1  0/6 (0.00%)  1/5 (20.00%) 
Dysgeusia  1  1/6 (16.67%)  0/5 (0.00%) 
Peripheral motor neuropathy  1  0/6 (0.00%)  1/5 (20.00%) 
Vascular disorders     
Hypotension  1  1/6 (16.67%)  0/5 (0.00%) 
Thromboembolic event  1  1/6 (16.67%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 4.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Statistician
Organization: ECOG Statistical Office
Phone: 617-632-3012
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01078454     History of Changes
Other Study ID Numbers: NCI-2011-02010
NCI-2011-02010 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E4A08 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: February 27, 2010
First Posted: March 2, 2010
Results First Submitted: November 20, 2014
Results First Posted: November 26, 2014
Last Update Posted: November 26, 2014