Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary 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.
Primary Systemic Amyloidosis
Light Chain Deposition Disease
Genetic: microarray analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
|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|
- Complete hematologic response [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||September 2007|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
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
Bortezomib 1.3 mg/m2 days 1, 8, 15, 22
Other Name: VelcadeDrug: dexamethasone
Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23
Other Names:Drug: melphalan
Melphalan 9 mg/m2/day days 1-4
Other Names:Genetic: microarray analysis
≤28 days prior to enrollmentOther: flow cytometry
Day 1 of cycles 6, 12, 18 and at end of study.Other: laboratory biomarker analysis
≤28 days prior to enrollmentProcedure: quality-of-life assessment
Start of each cycle
- Determine the complete hematologic response rate at 12 months.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00520767
|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|
|Principal Investigator:||Jeffrey A. Zonder, MD||Barbara Ann Karmanos Cancer Institute|