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

December 20, 2023 updated by: Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University Cancer Research Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Josephine Ford Cancer Center at Henry Ford Hospital
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Southfield, Michigan, United States, 48075
        • Providence Cancer Institute at Providence Hospital - Southfield Campus
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Cancer Centers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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
Drug: bortezomib
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
Other Names:
  • Velcade
Drug: dexamethasone
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
Other Names:
  • Decadron
  • Hexadrol
  • Dexasone
  • Dexamethasone Acetate
  • Maxidex
  • Dexamethasone Sodium Phosphate
  • Diodex
Drug: melphalan
Melphalan 9 mg/m2/day days 1-4
Other Names:
  • L-PAM
  • L-Sarcolysin
  • Phenylalanine Mustard
  • Alkeran®
Genetic: microarray analysis
≤28 days prior to enrollment
Other: flow cytometry
Day 1 of cycles 6, 12, 18 and at end of study.
Other: laboratory biomarker analysis
≤28 days prior to enrollment
Procedure: quality-of-life assessment
Start of each cycle

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Complete Hematologic Response
Time Frame: Up to 12 months
Up to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Organ Response Rate (OrR)
Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
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.
Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Overall Survival
Time Frame: time from day of registration until 72 months.
time from day of registration until day of death.
time from day of registration until 72 months.
Time to Treatment Failure (TTF)
Time Frame: start of treatment until 72 months
Time from start of treatment until date of documented disease progression, removal from protocol due to toxicity, or death from any cause.
start of treatment until 72 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Barbara Ann Karmanos Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeffrey A. Zonder, MD, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 6, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 24, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2007

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 27, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2006-132
  • P30CA022453 (U.S. NIH Grant/Contract)
  • MILLENNIUM-WSU-2006-132 (Barbara Ann Karmanos Cancer Institute)
  • WSU-HIC-060907M1F (Other Identifier: Wayne State University - Human Investigation Committee)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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