Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease
Condition: Primary Systemic Amyloidosis; Light Chain Deposition Disease
MeSH terms: Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Amyloidosis
Intervention: bortezomib; dexamethasone; melphalan; microarray analysis; flow cytometry; laboratory biomarker analysis; quality-of-life assessment
Intervention description: 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; ≤28 days prior to enrollment; Day 1 of cycles 6, 12, 18 and at end of study.; ≤28 days prior to enrollment; Start of each cycle
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Bortezomib; Melphalan; Dexamethasone 21-phosphate; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: primary systemic amyloidosis; light chain deposition disease

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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

        PATIENT CHARACTERISTICS:

          -  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

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No other investigational drugs within the past 14 days