A Phase 3 interventional study of melphalan and dexamethasone in Light Chain Deposition Disease and Primary Systemic Amyloidosis, sponsored by National Cancer Institute (NCI). Completed at 209 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-02-01.
Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment
This randomized phase III trial is studying melphalan and dexamethasone to see how well they work with or without bortezomib in treating patients with previously untreated systemic amyloidosis. Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of plasma cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving melphalan together with dexamethasone is more effective with or without bortezomib in treating systemic amyloidosis.
PRIMARY OBJECTIVES:
I. To compare hematologic overall response (partial response [PR], very good PR, amyloid complete hematologic response [ACR], and stringent complete response [sCR]) after 3 courses of therapy in patients with previously untreated systemic light-chain amyloidosis treated with melphalan and dexamethasone with vs without bortezomib.
SECONDARY OBJECTIVES:
I. To evaluate the ACR rate after 3 courses of therapy and at completion of therapy.
II. To evaluate organ response rates after 3 courses of therapy and at 6, 9, and 12 months.
III. To evaluate treatment-related mortality.
IV. To evaluate toxicity.
V. To evaluate progression-free and overall survival.
VI. To evaluate PR or better at completion of therapy.
VII. To evaluate time to hematologic and organ response.
VIII. To evaluate the duration of hematologic and organ response.
IX. To assess quality of life (QOL) at baseline, at 3, 6, and 9 months during the therapy, at completion of therapy, and 3 and 6 months after therapy.
TERTIARY OBJECTIVES:
I. To determine the prognostic impact of t(11;14) translocation and cyclin D1 overexpression on response and overall survival.
II. (Correlative) To compare sCR rates and to determine the impact of sCR on the outcomes.
III. (Correlative) To perform a descriptive analysis of amyloid typing and proteomic composition of amyloid tissues.
OUTLINE: This is a multicenter study. Patients are stratified according to amyloid cardiac stage (stage I/II vs. better risk stage III) and are randomized to 1 of 2 treatment arms.
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/m2 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, urine, bone marrow, and fat samples may be collected periodically for laboratory analysis. Health-related quality of life is assessed periodically before, during, and after therapy. After completion of study treatment, patients are followed up periodically for 5 years.
174 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 58 are open to participants now.
This study's enrollment of 11 is below the median of 37 across 124 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.
Browse Immunoglobulin Light-chain Amyloidosis studies →National Cancer Institute (NCI) is the lead sponsor of 3,554 studies on the registry; 334 are open to participants now.
Of its 407 completed or terminated interventional studies of FDA-regulated products, 370 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Histologically confirmed diagnosis of systemic light-chain amyloidosis
Measurable disease, defined by >= 1 of the following:
Symptomatic organ involvement* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:
Amyloid cardiac biomarker stage I or II disease
Human immunodeficiency virus (HIV)-positivity allowed provided the following criteria are met:
More than 3 weeks since radiotherapy
Exclusion Criteria:
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.
Drug: melphalan · Drug: dexamethasone
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.
Drug: melphalan · Drug: dexamethasone · Drug: bortezomib
Given PO
Also known as: L-PAM, L-phenylalanine mustard, L-sarcolysin, Alkeran, NSC #8806
Given PO
Also known as: Decadron, Hexadrol, Dexameth, Dexone, DXM
Given IV
Also known as: Velcade®, PS-341, MLN-341, LDP-341
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
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
Participants were recruited from ECOG member institutions between November 1, 2010 and September 7, 2012.
| Milestone | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) |
|---|---|---|
| Started | 6 | 5 |
| Completed | 5 | 3 |
| Not completed | 1 | 2 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Death | 0 | 1 |
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
| Proportion of patients | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) |
|---|---|---|
| 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 (0.06 to 0.73) | 0.60 (0.19 to 0.92) |
Collected over Assessed every 4 weeks while on treatment and for 30 days after the end of treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (Mel-Dex) | — | 1/6 (16.7%) | 1/6 (16.7%) |
| Arm B (B-Mel-Dex) | — | 3/5 (60%) | 5/5 (100%) |
| Event | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) |
|---|---|---|
| Platelet count decreasedInvestigations | 1/6 | 1/5 |
| HypocalcemiaMetabolism and nutrition disorders | 0/6 | 1/5 |
| Generalized muscle weaknessMusculoskeletal and connective tissue disorders | 1/6 | 1/5 |
| FatigueGeneral disorders | 1/6 | 0/5 |
| Neutrophil count decreasedInvestigations | 1/6 | 0/5 |
| White blood cell decreasedInvestigations | 1/6 | 0/5 |
| AnorexiaMetabolism and nutrition disorders | 1/6 | 0/5 |
| DehydrationMetabolism and nutrition disorders | 1/6 | 0/5 |
| HypokalemiaMetabolism and nutrition disorders | 1/6 | 0/5 |
| HypotensionVascular disorders | 1/6 | 0/5 |
| Event | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) |
|---|---|---|
| FatigueGeneral disorders | 1/6 | 2/5 |
| NauseaGastrointestinal disorders | 1/6 | 2/5 |
| Generalized muscle weaknessMusculoskeletal and connective tissue disorders | 0/6 | 2/5 |
| AnemiaBlood and lymphatic system disorders | 1/6 | 1/5 |
| ConstipationGastrointestinal disorders | 0/6 | 1/5 |
| DiarrheaGastrointestinal disorders | 0/6 | 1/5 |
| Lung infectionInfections and infestations | 0/6 | 1/5 |
| Platelet count decreasedInvestigations | 0/6 | 1/5 |
| AnorexiaMetabolism and nutrition disorders | 1/6 | 1/5 |
| HyperglycemiaMetabolism and nutrition disorders | 0/6 | 1/5 |
All enrolled patients are included in this analysis.
| Age, Continuous(years) | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) | Total |
|---|---|---|---|
| Median | 68 (61 to 78) | 66 (44 to 72) | 67 (44 to 78) |
| Sex: Female, Male(Participants) | Arm A (Mel-Dex) | Arm B (B-Mel-Dex) | Total |
|---|---|---|---|
| Female | 3 | 2 | 5 |
| Male | 3 | 3 | 6 |
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This study is completed, as verified in Jan 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Bortezomib
Immunoglobulin Light-chain Amyloidosis →
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