Primary Systemic AmyloidosisPhase 2NCT00520767
Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease
A Phase 2 study testing bortezomib, dexamethasone and melphalan in people with Primary Systemic Amyloidosis and Light Chain Deposition Disease, run by Barbara Ann Karmanos Cancer Institute at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Primary Systemic Amyloidosis, Light Chain Deposition Disease
- What is being tested?
- bortezomib, dexamethasone and melphalan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2007to 6 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Boston University Cancer Research Center
Boston, Massachusetts, 02118
Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
Denver, Colorado, 80218
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201-1379
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, 48075
About this study
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
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.
Read the 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.
- Being tested
- bortezomib, dexamethasone, melphalan, microarray analysis, flow cytometry
- Keywords
- primary systemic amyloidosis, light chain deposition disease
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called Velcade
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
dexamethasoneDrug
Also called Dexasone, Decadron, Diodex, Hexadrol
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
melphalanDrug
Also called Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine Mustard
Melphalan 9 mg/m2/day days 1-4
microarray analysisGenetic
≤28 days prior to enrollment
flow cytometryOther
Day 1 of cycles 6, 12, 18 and at end of study.
laboratory biomarker analysisOther
≤28 days prior to enrollment
quality-of-life assessmentProcedure or surgery
Start of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Melphalan, Dexamethasone, Bortezomib, | 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 Receives: Drug: bortezomib; Drug: dexamethasone; Drug: melphalan; Genetic: microarray analysis; Other: flow cytometry; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Hematologic Response
Measured: Up to 12 months
Secondary outcomes (4)
Overall Survival
time from day of registration until day of death.
Measured: time from day of registration until 72 months.
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.
Measured: start of treatment until 72 months
Organ Response Rate (OrR)
Measured: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Overall Hematologic Response Rate (OHR)
Measured: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2007 (estimated)
- Study startSep 2007
- Primary completionOct 2010
- Study completion6 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Systemic AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute
- Investigators
- Jeffrey A. Zonder, MD, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00520767
- Sponsor's protocol ID
- 2006-132
- Other IDs
- P30CA022453, MILLENNIUM-WSU-2006-132, WSU-HIC-060907M1F
- Status last verified
- Dec 2023
- First submitted
- 24 Aug 2007
- Last updated
- 22 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00520767
- Acronym / sponsor ID
- 2006-132
- Keywords
- primary systemic amyloidosis, light chain deposition disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2007
- Primary completion
- Oct 2010 (actual)
- Study completion
- 6 Jun 2019 (actual)
- First posted
- 27 Aug 2007 (estimated)
- Results
- Posted 30 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Melphalan, Dexamethasone, Bortezomib, | Experimental | Drug: bortezomib, Drug: dexamethasone, Drug: melphalan, Genetic: microarray analysis, Other: flow cytometry, Other: laboratory biomarker analysis, Procedure: quality-of-life assessmentBortezomib 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 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomibAlso: VelcadeBortezomib 1.3 mg/m2 days 1, 8, 15, 22 | Drug | Melphalan, Dexamethasone, Bortezomib, |
| dexamethasoneAlso: Dexasone, Decadron, Diodex, HexadrolDexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23 | Drug | Melphalan, Dexamethasone, Bortezomib, |
| melphalanAlso: Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine MustardMelphalan 9 mg/m2/day days 1-4 | Drug | Melphalan, Dexamethasone, Bortezomib, |
| microarray analysis≤28 days prior to enrollment | Genetic | Melphalan, Dexamethasone, Bortezomib, |
| flow cytometryDay 1 of cycles 6, 12, 18 and at end of study. | Other | Melphalan, Dexamethasone, Bortezomib, |
| laboratory biomarker analysis≤28 days prior to enrollment | Other | Melphalan, Dexamethasone, Bortezomib, |
| quality-of-life assessmentStart of each cycle | Procedure or surgery | Melphalan, Dexamethasone, Bortezomib, |
Primary outcome
Complete Hematologic Response
Time frame: Up to 12 months
4 secondary outcomes
Overall Survival
Time frame: time from day of registration until 72 months.
Time to Treatment Failure (TTF)
Time frame: start of treatment 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Clinical trial summary from the National Cancer Institute's PDQ® databaseLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey A. Zonder, MD principal investigator
Barbara Ann Karmanos Cancer Institute
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bortezomib, dexamethasone and melphalan in people with Primary Systemic Amyloidosis and Light Chain Deposition Disease, run by Barbara Ann Karmanos Cancer Institute at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Hematologic Response (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2023; AzTrials last refreshed its copy on 7 Nov 2026.