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

Information source: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Primary Systemic Amyloidosis; Light Chain Deposition Disease

Intervention: bortezomib (Drug); dexamethasone (Drug); melphalan (Drug); microarray analysis (Genetic); flow cytometry (Other); laboratory biomarker analysis (Other); quality-of-life assessment (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: Barbara Ann Karmanos Cancer Institute

Official(s) and/or principal investigator(s):
Jeffrey A. Zonder, MD, Principal Investigator, Affiliation: Barbara Ann Karmanos Cancer Institute

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.

Clinical Details

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

Primary outcome: Complete Hematologic Response

Secondary outcome:

Overall Survival

Time to Treatment Failure

Change in Quality of Life From Baseline as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Questionnaire.

Organ Response Rate (OrR)

Toxicity, Including Neurotoxicity

Overall Hematologic Response Rate (OHR)

Detailed 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program, Denver, Colorado 80218, United States

Boston University Cancer Research Center, Boston, Massachusetts 02118, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Josephine Ford Cancer Center at Henry Ford Hospital, Detroit, Michigan 48202, United States

Providence Cancer Institute at Providence Hospital - Southfield Campus, Southfield, Michigan 48075, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

UPMC Cancer Centers, Pittsburgh, Pennsylvania 15232, United States

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: September 2007
Last updated: March 18, 2015

Page last updated: August 23, 2015

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