search
Back to results

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

Primary Purpose

Primary Systemic Amyloidosis, Light Chain Deposition Disease

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
dexamethasone
melphalan
microarray analysis
flow cytometry
laboratory biomarker analysis
quality-of-life assessment
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Systemic Amyloidosis focused on measuring primary systemic amyloidosis, light chain deposition disease

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
  • Boston University Cancer Research Center
  • Barbara Ann Karmanos Cancer Institute
  • Josephine Ford Cancer Center at Henry Ford Hospital
  • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Duke Comprehensive Cancer Center
  • UPMC Cancer Centers

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Melphalan, Dexamethasone, Bortezomib,

Arm 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

Outcomes

Primary Outcome Measures

Complete Hematologic Response

Secondary Outcome Measures

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)

Full Information

First Posted
August 24, 2007
Last Updated
August 24, 2022
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00520767
Brief Title
Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease
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 Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 2007 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
May 9, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Systemic Amyloidosis, Light Chain Deposition Disease
Keywords
primary systemic amyloidosis, light chain deposition disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Melphalan, Dexamethasone, Bortezomib,
Arm Type
Experimental
Arm 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 Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Dexasone, Decadron, Diodex, Hexadrol, Maxidex, Dexamethasone Sodium Phosphate, Dexamethasone Acetate
Intervention Description
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine Mustard
Intervention Description
Melphalan 9 mg/m2/day days 1-4
Intervention Type
Genetic
Intervention Name(s)
microarray analysis
Intervention Description
≤28 days prior to enrollment
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Day 1 of cycles 6, 12, 18 and at end of study.
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
≤28 days prior to enrollment
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Intervention Description
Start of each cycle
Primary Outcome Measure Information:
Title
Complete Hematologic Response
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
Day 1 of Each Cycle and every 12 weeks after last treatment cycle
Title
Time to Treatment Failure
Time Frame
Day 1 of Each Cycle
Title
Change in Quality of Life From Baseline as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Questionnaire.
Time Frame
At the start of each cycle
Title
Organ Response Rate (OrR)
Time Frame
Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Title
Toxicity, Including Neurotoxicity
Time Frame
Day 1 of Each Cycle
Title
Overall Hematologic Response Rate (OHR)
Time Frame
Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey A. Zonder, MD
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Boston University Cancer Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-1379
Country
United States
Facility Name
Josephine Ford Cancer Center at Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Providence Cancer Institute at Providence Hospital - Southfield Campus
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
UPMC Cancer Centers
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Links:
URL
http://cancer.gov/clinicaltrials
Description
Clinical trial summary from the National Cancer Institute's PDQ® database

Learn more about this trial

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

We'll reach out to this number within 24 hrs