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A Multicenter Phase II Trial of Bortezomib (Velcade), Melphalan, and Dexamethasone (V-MD) in Patients With Symptomatic AL-Amyloidosis or Light Chain Deposition Disease

Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

A Multicenter Phase II Trial of Bortezomib (Velcade), Melphalan, and Dexamethasone (V-MD) in Patients With Symptomatic AL-Amyloidosis or Light Chain Deposition Disease



- 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

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.

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete hematologic response

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Jeffrey A. Zonder, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2007

Completion Date:

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • primary systemic amyloidosis
  • refractory multiple myeloma
  • Amyloidosis
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan  48202
UPMC Cancer Centers Pittsburgh, Pennsylvania  15232
Providence Cancer Institute at Providence Hospital - Southfield Campus Southfield, Michigan  48075
Boston University Cancer Research Center Boston, Massachusetts  02118
Sinai-Grace Hospital Detroit, Michigan  48235
Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program Denver, Colorado  80218