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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey Zonder, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00520767
First received: August 24, 2007
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Primary Systemic Amyloidosis
Light Chain Deposition Disease
Drug: bortezomib
Drug: dexamethasone
Drug: melphalan
Genetic: microarray analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Complete hematologic response [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Day 1 of Each Cycle and every 12 weeks after last treatment cycle ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Day 1 of Each Cycle ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Organ Response Rate (OrR) [ Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study. ] [ Designated as safety issue: No ]
  • Toxicity, including neurotoxicity [ Time Frame: Day 1 of Each Cycle ] [ Designated as safety issue: Yes ]
  • Overall Hematologic Response Rate (OHR) [ Time Frame: Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study. ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: September 2007
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Velcade
Drug: dexamethasone
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
Other Names:
  • Dexasone
  • Decadron
  • Diodex
  • Hexadrol
  • Maxidex
  • Dexamethasone Sodium Phosphate
  • Dexamethasone Acetate
Drug: melphalan
Melphalan 9 mg/m2/day days 1-4
Other Names:
  • Alkeran®
  • L-PAM
  • L-Sarcolysin
  • Phenylalanine Mustard
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00520767

Locations
United States, Colorado
Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program
Denver, Colorado, United States, 80218
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, United States, 48075
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Jeffrey A. Zonder, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Jeffrey Zonder, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00520767     History of Changes
Other Study ID Numbers: CDR0000555016, P30CA022453, WSU-2006-132, MILLENNIUM-WSU-2006-132, WSU-HIC-060907M1F
Study First Received: August 24, 2007
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
primary systemic amyloidosis
light chain deposition disease

Additional relevant MeSH terms:
Amyloidosis
Multiple Myeloma
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Melphalan
Sodium phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014