Skip to content

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

A Multicenter Phase II Trial of Bortezomib (Velcade), Melphalan, and Dexamethasone (V-MD) in Patients With Symptomatic AL-Amyloidosis or Light Chain Deposition Disease

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00520767
Enrollment
35
Registered
2007-08-27
Start date
2007-09-30
Completion date
2019-06-06
Last updated
2023-12-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Light Chain Deposition Disease, Primary Systemic Amyloidosis

Keywords

primary systemic amyloidosis, light chain deposition disease

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.

Interventions

DRUGbortezomib

Bortezomib 1.3 mg/m2 days 1, 8, 15, 22

DRUGdexamethasone

Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23

DRUGmelphalan

Melphalan 9 mg/m2/day days 1-4

GENETICmicroarray analysis

≤28 days prior to enrollment

OTHERflow cytometry

Day 1 of cycles 6, 12, 18 and at end of study.

OTHERlaboratory biomarker analysis

≤28 days prior to enrollment

PROCEDUREquality-of-life assessment

Start of each cycle

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Barbara Ann Karmanos Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frame
Complete Hematologic ResponseUp to 12 months

Secondary

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

Countries

United States

Participant flow

Participants by arm

ArmCount
Melphalan, Dexamethasone, Bortezomib,
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: Bortezomib 1.3 mg/m2 days 1, 8, 15, 22 dexamethasone: Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23 melphalan: 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
35
Total35

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDeath2

Baseline characteristics

CharacteristicMelphalan, Dexamethasone, Bortezomib,
Age, Continuous64 years
Region of Enrollment
United States
35 participants
Sex: Female, Male
Female
15 Participants
Sex: Female, Male
Male
20 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
3 / 35
serious
Total, serious adverse events
12 / 35

Outcome results

Primary

Complete Hematologic Response

Time frame: Up to 12 months

Population: Individuals evaluable for response

ArmMeasureValue (NUMBER)
Melphalan, Dexamethasone, Bortezomib,Complete Hematologic Response16 participants
Secondary

Organ Response Rate (OrR)

Time frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

Population: Not collected not analyzed.

Secondary

Overall Hematologic Response Rate (OHR)

Time frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

Population: Not collected not analyzed.

Secondary

Overall Survival

time from day of registration until day of death.

Time frame: time from day of registration until 72 months.

ArmMeasureValue (MEDIAN)
Melphalan, Dexamethasone, Bortezomib,Overall Survival31.1 month
Secondary

Time to Treatment Failure (TTF)

Time from start of treatment until date of documented disease progression, removal from protocol due to toxicity, or death from any cause.

Time frame: start of treatment until 72 months

ArmMeasureValue (MEDIAN)
Melphalan, Dexamethasone, Bortezomib,Time to Treatment Failure (TTF)18.1 month

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026