NCT00520767 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2023-12-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Complete Hematologic Response

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outcome · POSTED

Overall Survival

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outcome · POSTED

Time to Treatment Failure (TTF)

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outcome · POSTED

Organ Response Rate (OrR)

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outcome · POSTED

Overall Hematologic Response Rate (OHR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 120 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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
intervention Names
Drug: bortezomib
Drug: dexamethasone
Drug: melphalan
Genetic: microarray analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
label
Melphalan, Dexamethasone, Bortezomib,
type
EXPERIMENTAL

interventions

arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
name
bortezomib
other Names
Velcade
type
DRUG
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
name
dexamethasone
other Names
Dexasone
Decadron
Diodex
Hexadrol
Maxidex
Dexamethasone Sodium Phosphate
Dexamethasone Acetate
type
DRUG
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
Melphalan 9 mg/m2/day days 1-4
name
melphalan
other Names
Alkeran®
L-PAM
L-Sarcolysin
Phenylalanine Mustard
type
DRUG
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
≤28 days prior to enrollment
name
microarray analysis
type
GENETIC
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
Day 1 of cycles 6, 12, 18 and at end of study.
name
flow cytometry
type
OTHER
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
≤28 days prior to enrollment
name
laboratory biomarker analysis
type
OTHER
arm Group Labels
Melphalan, Dexamethasone, Bortezomib,
description
Start of each cycle
name
quality-of-life assessment
type
PROCEDURE

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 35
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

measure
Complete Hematologic Response
time Frame
Up to 12 months

secondary Outcomes

description
time from day of registration until day of death.
measure
Overall Survival
time Frame
time from day of registration until 72 months.
description
Time from start of treatment until date of documented disease progression, removal from protocol due to toxicity, or death from any cause.
measure
Time to Treatment Failure (TTF)
time Frame
start of treatment until 72 months
measure
Organ Response Rate (OrR)
time Frame
Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
measure
Overall Hematologic Response Rate (OHR)
time Frame
Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

Full study description

brief 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.
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. * 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.

Source references