Overview

This trial is active, not recruiting.

Conditions primary systemic amyloidosis, light chain deposition disease
Treatments bortezomib, dexamethasone, melphalan, microarray analysis, flow cytometry, laboratory biomarker analysis, quality-of-life assessment
Phase phase 2
Target proteasome
Sponsor Barbara Ann Karmanos Cancer Institute
Collaborator National Cancer Institute (NCI)
Start date September 2007
End date December 2013
Trial size 35 participants
Trial identifier NCT00520767, CDR0000555016, MILLENNIUM-WSU-2006-132, P30CA022453, WSU-2006-132, WSU-HIC-060907M1F

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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
bortezomib Velcade
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
dexamethasone Dexasone
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
melphalan Alkeran®
Melphalan 9 mg/m2/day days 1-4
microarray analysis
≤28 days prior to enrollment
flow cytometry
Day 1 of cycles 6, 12, 18 and at end of study.
laboratory biomarker analysis
≤28 days prior to enrollment
quality-of-life assessment
Start of each cycle

Primary Outcomes

Measure
Complete hematologic response
time frame: Up to 12 months

Secondary Outcomes

Measure
Overall survival
time frame: Day 1 of Each Cycle and every 12 weeks after last treatment cycle
Time to treatment failure
time frame: Day 1 of Each Cycle
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
Organ Response Rate (OrR)
time frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Toxicity, including neurotoxicity
time frame: Day 1 of Each Cycle
Overall Hematologic Response Rate (OHR)
time frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Jeffrey A. Zonder, MD
Description OBJECTIVES: Primary - Determine the complete hematologic response rate at 12 months. Secondary - 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2013.
Information provided to ClinicalTrials.gov by Barbara Ann Karmanos Cancer Institute.