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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT00520767
• Date of registration: 24/08/2007
• Prospective Registration: Yes
• Primary sponsor: Barbara Ann Karmanos Cancer Institute
• Public title: Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease
• Scientific 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
• Date of first enrolment: September 2007
• Target sample size: 35
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT00520767
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Jeffrey A. Zonder, MD
• Affiliation: Barbara Ann Karmanos Cancer Institute

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 120 Years
Gender: All

Health Condition(s) or Problem(s) studied

Light Chain Deposition Disease

Primary Systemic Amyloidosis

Intervention(s)

Other: flow cytometry

Procedure: quality-of-life assessment

Drug: bortezomib

Drug: dexamethasone

Genetic: microarray analysis

Other: laboratory biomarker analysis

Drug: melphalan

Primary Outcome(s)

Complete Hematologic Response [Time Frame: Up to 12 months]

Secondary Outcome(s)

Overall Survival [Time Frame: time from day of registration until 72 months.]

Organ Response Rate (OrR) [Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.]

Overall Hematologic Response Rate (OHR) [Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.]

Time to Treatment Failure (TTF) [Time Frame: start of treatment until 72 months]

Secondary ID(s)

MILLENNIUM-WSU-2006-132

P30CA022453

2006-132

WSU-HIC-060907M1F

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Results

• Results available: Yes
• Date Posted: 30/03/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00520767