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

Completed · Phase 3

Conditions studied: Light Chain Deposition Disease, Primary Systemic Amyloidosis

In brief

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.

Key facts

Study ID

NCT01078454

Run by

National Cancer Institute (NCI)

People needed

11

Starts

2010-11-01

Expected to finish

2012-11-27

Last updated by the study team

2022-02-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed diagnosis of systemic light-chain amyloidosis
• Histologic diagnosis of disease must be confirmed by pathology (positive Congo red stain with green birefringence on polarized light microscopy)
• Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis (required in patients who are African-American or who present with peripheral neuropathy as the dominant organ involvement)
• Measurable disease, defined by >= 1 of the following:
• Serum M-protein >= 1 g/dL by serum protein electrophoresis (SPEP)
• Difference between involved and uninvolved free light chain be >4.0mg/dL provided the kappa to lambda free light chain (FLC) ratio is abnormal
• Symptomatic organ involvement* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:
• NOTE: *Carpal tunnel syndrome skin purpura or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
• Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day by 24-hour urine collection
• Cardiac involvement is defined as the presence of a mean left ventricular wall thickness of > 12 mm by echocardiogram in the absence of a history of hypertension or valvular heart disease or in the presence of unexplained low voltage (< 0.5 mV) by electrocardiogram
• Hepatic involvement is defined as hepatomegaly or an alkaline phosphatase > 1.5 times upper limit of normal (ULN)
• Peripheral nerve involvement is defined by clinical history or abnormal sensory and/or motor findings on neurologic exam
• Gastrointestinal (GI) involvement is defined as gross GI bleeding or diarrhea (at least 4 stools per day over baseline); a positive GI biopsy is not sufficient to document clinical involvement
• Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea, or constipation
• Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy
• Ineligible for autologous stem cell transplantation with melphalan 200 mg/m\^2 or refuses to undergo transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Amyloid cardiac biomarker stage I or II disease
• The amyloid cardiac staging system is based on NT-proBNP and troponin-T levels. If troponin T (cTnT) is not available at local institution then troponin I (cTnI) may be used. Thresholds for cTnT, cTnI, and NT-proBNP are < 0.035 ug/L, < 0.1 ug/L, and < 332 ng/L, respectively. Stage I patients have both troponin-T (or I) and NT-proBNP below the threshold. Stage II patients have either troponin-T (I) or NT-proBNP above the threshold. Stage III patients have troponin-T (or I) and simultaneous NT-proBNP above the threshold. Stage III patients are further classified as "better risk" if NT-proBNP is over 332 ng/L but less than 6000 ng/L
• Negative pregnancy test
• Fertile patients must use effective contraception
• The absence of supine systolic blood pressure < 100 mmHg and difficult to manage symptomatic orthostatic hypotension
• Absolute neutrophil count (ANC) > 1,500/mm\^3
• Platelet count > 140,000/mm\^3
• Hemoglobin > 10 g/dL

You may not qualify if…

• Pregnant or nursing
• Clinically overt myeloma (hypercalcemia or lytic bone lesions)
• Prior chemotherapy or radiotherapy for the treatment of myeloma or systemic light-chain amyloidosis
• History of sustained ventricular tachycardias
• Cardiac syncope
• Uncompensated New York Heart Association (NYHA) class III or IV congestive heart failure
• Uncontrolled infection
• Active malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I cancer currently in complete remission
• Serious medical or psychiatric illness likely to interfere with study participation, including recent myocardial infarction (within the past 6 months) or poorly controlled diabetes mellitus
• Hypersensitivity to bortezomib, boron, or mannitol
• Grade 2 or higher peripheral neuropathy

Where it is running

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• The Medical Center of Aurora — Aurora, Colorado, United States
• Boulder Community Hospital — Boulder, Colorado, United States
• Penrose-Saint Francis Healthcare — Colorado Springs, Colorado, United States
• Porter Adventist Hospital — Denver, Colorado, United States
• Exempla Saint Joseph Hospital — Denver, Colorado, United States
• Presbyterian - Saint Lukes Medical Center - Health One — Denver, Colorado, United States
• Rose Medical Center — Denver, Colorado, United States
• Colorado Cancer Research Program CCOP — Denver, Colorado, United States
• Swedish Medical Center — Englewood, Colorado, United States
• Saint Mary's Hospital and Regional Medical Center — Grand Junction, Colorado, United States
• North Colorado Medical Center — Greeley, Colorado, United States
• Saint Anthony Hospital — Lakewood, Colorado, United States
• Littleton Adventist Hospital — Littleton, Colorado, United States
• Sky Ridge Medical Center — Lone Tree, Colorado, United States
• Longmont United Hospital — Longmont, Colorado, United States
• McKee Medical Center — Loveland, Colorado, United States
• Parker Adventist Hospital — Parker, Colorado, United States
• Saint Mary Corwin Medical Center — Pueblo, Colorado, United States
• North Suburban Medical Center — Thornton, Colorado, United States
• Exempla Lutheran Medical Center — Wheat Ridge, Colorado, United States
• Eastern Connecticut Hematology and Oncology Associates — Norwich, Connecticut, United States
• Beebe Medical Center — Lewes, Delaware, United States
• Christiana Care Health System-Christiana Hospital — Newark, Delaware, United States
• Mayo Clinic in Arizona — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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