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Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00520767
Recruitment Status : Active, not recruiting
First Posted : August 27, 2007
Results First Posted : March 30, 2015
Last Update Posted : February 22, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute

Brief Summary:

RATIONALE: Giving bortezomib together with melphalan and dexamethasone may be an effective treatment for primary amyloidosis and light chain deposition disease.

PURPOSE: This phase II trial is studying how well giving bortezomib together with melphalan and dexamethasone works in treating patients with primary amyloidosis or light chain deposition disease.

Condition or disease Intervention/treatment Phase
Primary Systemic Amyloidosis Light Chain Deposition Disease Drug: bortezomib Drug: dexamethasone Drug: melphalan Genetic: microarray analysis Other: flow cytometry Other: laboratory biomarker analysis Procedure: quality-of-life assessment Phase 2

Detailed Description:



  • Determine the complete hematologic response rate at 12 months.


  • Determine the overall hematologic response rate.
  • Determine the organ response rate.
  • Determine time to treatment failure.
  • Assess toxicity of the regimen, in terms of incidence and severity of treatment-emergent peripheral neuropathy and quality of life.
  • Determine the overall survival.

OUTLINE: This is a multicenter study.

Patients receive oral melphalan on days 1-4, bortezomib IV on days 1, 8, 15, and 22, and dexamethasone orally or IV on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 4-6 weeks for up to 20 courses in the absence of disease progression or unacceptable toxicity.

Blood, urine, and bone marrow aspirates are collected at baseline and periodically after treatment to permit the correlation of clinical results with measured molecular events. A single baseline peripheral blood DNA sample is collected for future association studies linking disease onset, progression, and response to administered therapy with single nucleotide polymorphisms. Blood plasma and urine samples are evaluated for proteomic markers associated with disease progression and therapeutic response. Peripheral blood RNA samples are evaluated for transcriptional response to treatment of peripheral blood lymphocytes. Bone marrow aspirates are collected to extract plasma cells by flow cytometry for gene expression profiling.

Quality of life is assessed at the beginning of each course.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Trial of Bortezomib (Velcade), Melphalan, and Dexamethasone (V-MD) in Patients With Symptomatic AL-Amyloidosis or Light Chain Deposition Disease
Study Start Date : September 2007
Actual Primary Completion Date : October 2010
Estimated Study Completion Date : June 2019

Arm Intervention/treatment
Experimental: Melphalan, Dexamethasone, Bortezomib,
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22; Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23; Melphalan 9 mg/m2/day days 1-4
Drug: bortezomib
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
Other Name: Velcade

Drug: dexamethasone
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
Other Names:
  • Dexasone
  • Decadron
  • Diodex
  • Hexadrol
  • Maxidex
  • Dexamethasone Sodium Phosphate
  • Dexamethasone Acetate

Drug: melphalan
Melphalan 9 mg/m2/day days 1-4
Other Names:
  • Alkeran®
  • L-PAM
  • L-Sarcolysin
  • Phenylalanine Mustard

Genetic: microarray analysis
≤28 days prior to enrollment

Other: flow cytometry
Day 1 of cycles 6, 12, 18 and at end of study.

Other: laboratory biomarker analysis
≤28 days prior to enrollment

Procedure: quality-of-life assessment
Start of each cycle

Primary Outcome Measures :
  1. Complete Hematologic Response [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Day 1 of Each Cycle and every 12 weeks after last treatment cycle ]
  2. Time to Treatment Failure [ Time Frame: Day 1 of Each Cycle ]
  3. Change in Quality of Life From Baseline as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Questionnaire. [ Time Frame: At the start of each cycle ]
  4. Organ Response Rate (OrR) [ Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study. ]
  5. Toxicity, Including Neurotoxicity [ Time Frame: Day 1 of Each Cycle ]
  6. Overall Hematologic Response Rate (OHR) [ Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Biopsy-proven diagnosis of 1 of the following:

    • Primary systemic amyloidosis

      • Histochemical diagnosis of amyloidosis determined by polarizing microscopy of green bi-refringent material in Congo red-stained tissue specimens or characteristic electron microscopy appearance
    • Light chain deposition disease
  • Measurable disease as defined by one or more of the following:

    • Serum monoclonal protein ≥ 0.5 g/dL by serum electrophoresis
    • Urine monoclonal protein > 200 mg/tv in a 24 hr urine electrophoresis
    • Serum immunoglobulin free-light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa lambda free light chain ratio
  • Must meet 1 of the following criteria:

    • Clonal population of plasma cells in the bone marrow (≤ 30%)
    • Immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils
  • Must not meet the following diagnostic criteria for symptomatic* multiple myeloma:

    • Lytic lesions on skeletal survey
    • Plasmacytoma
    • Increase in bone marrow plasma cells ≥ 30% NOTE: *Patients who meet the International Myeloma Working Group definition of symptomatic multiple myeloma with symptoms attributable only to associated amyloidosis and who do not otherwise meet the criteria for diagnosis of smoldering myeloma are potentially eligible upon approval of the principal investigator.
  • If not previously treated, patient is either not a candidate for autologous stem cell transplantation (ASCT) or has declined the option of ASCT

    • Patients who have undergone prior ASCT and have subsequently progressed are eligible, provided other eligibility criteria are met
  • No secondary or familial amyloidosis


  • ECOG performance status 0-3
  • Creatinine < 5 mg/dL
  • Bilirubin < 2.5 times upper limit of normal (ULN)
  • ALT and AST < 3 times ULN
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 80,000/mm³
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Peripheral sensory neuropathy < grade 3
  • No myocardial infarction within the past 6 months
  • No New York Heart Association class III or IV heart failure
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No EKG* evidence of acute ischemia or active conduction system abnormalities (not including 1st degree AV-block, Wenckebach type 2nd degree heart block, or left bundle branch block) NOTE: *Prior to study entry, any EKG screening abnormality must be documented by the investigator as not medically relevant; there is no lower limit of LVEF below which patients are excluded from participation
  • No hypersensitivity to bortezomib, boron, or any of the other agents utilized in this study
  • No serious concurrent illness (e.g., stroke) within the past 30 days
  • No psychiatric illness likely to interfere with study participation
  • No untreated HIV infection

    • Patients with asymptomatic HIV infection on active antiretroviral therapy are potentially eligible
  • No diagnosis or treatment of another malignancy within the past 3 years, except completely resected basal cell or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy


  • See Disease Characteristics
  • No other investigational drugs within the past 14 days

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00520767

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United States, Colorado
Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
Denver, Colorado, United States, 80218
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, United States, 48075
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
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Principal Investigator: Jeffrey A. Zonder, MD Barbara Ann Karmanos Cancer Institute

Additional Information:
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Responsible Party: Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute Identifier: NCT00520767     History of Changes
Other Study ID Numbers: CDR0000555016
P30CA022453 ( U.S. NIH Grant/Contract )
WSU-2006-132 ( Other Identifier: Barbara Ann Karmanos Cancer Institute )
WSU-HIC-060907M1F ( Other Identifier: Wayne State University - Human Investigation Committee )
First Posted: August 27, 2007    Key Record Dates
Results First Posted: March 30, 2015
Last Update Posted: February 22, 2019
Last Verified: February 2019
Keywords provided by Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute:
primary systemic amyloidosis
light chain deposition disease
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Immunosuppressive Agents
Multiple Myeloma
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs