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

NCT00520767 | Completed Phase 2 Results DMC

• 4 other identifiers: 2006-132P30CA022453MILLENNIUM-WSU-2006-132WSU-HIC-060907M1F
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 7

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.

Conditions

Primary Systemic Amyloidosis; Light Chain Deposition Disease

Keywords

primary systemic amyloidosis; light chain deposition disease

Outcome Measures

Primary Outcomes (1)

• Complete Hematologic Response

  Up to 12 months

Secondary Outcomes (4)

• Overall Survival

  time from day of registration until 72 months.

• Time to Treatment Failure (TTF)

  start of treatment until 72 months

• Organ Response Rate (OrR)

  Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

• Overall Hematologic Response Rate (OHR)

  Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.

Study Arms (1)

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

Drug: bortezomib; Drug: dexamethasone; Drug: melphalan; Genetic: microarray analysis; Other: flow cytometry; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Interventions

bortezomib DRUG

Bortezomib 1.3 mg/m2 days 1, 8, 15, 22

Also known as: Velcade

Melphalan, Dexamethasone, Bortezomib,

dexamethasone DRUG

Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23

Also known as: Dexasone, Decadron, Diodex, Hexadrol, Maxidex, Dexamethasone Sodium Phosphate, Dexamethasone Acetate

Melphalan, Dexamethasone, Bortezomib,

melphalan DRUG

Melphalan 9 mg/m2/day days 1-4

Also known as: Alkeran®, L-PAM, L-Sarcolysin, Phenylalanine Mustard

Melphalan, Dexamethasone, Bortezomib,

microarray analysis GENETIC

≤28 days prior to enrollment

Melphalan, Dexamethasone, Bortezomib,

flow cytometry OTHER

Day 1 of cycles 6, 12, 18 and at end of study.

Melphalan, Dexamethasone, Bortezomib,

laboratory biomarker analysis OTHER

≤28 days prior to enrollment

Melphalan, Dexamethasone, Bortezomib,

quality-of-life assessment PROCEDURE

Start of each cycle

Melphalan, Dexamethasone, Bortezomib,

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program

Denver, Colorado, 80218, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Providence Cancer Institute at Providence Hospital - Southfield Campus

Southfield, Michigan, 48075, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; dexamethasone 21-phosphate; dexamethasone acetate; Melphalan; Microarray Analysis; Flow Cytometry

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Microchip Analytical Procedures; Investigative Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Limitations and Caveats

Mix of previously treated \& newly diagnosed pts (populations which may have different prognoses), plus the relatively small trial size limit conclusions one can draw re: relative efficacy of MDV (vs CyBorD or Mel-Dex, for example)

Results Point of Contact

• Title: Jeffrey Zonder, M.D.
• Organization: Barbara Ann Karmanos Cancer Institute

zonderj@karmanos.org

313-576-8732

Study Officials

• Jeffrey A. Zonder, MD

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2007
• First Posted: August 27, 2007
• Study Start: September 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: June 6, 2019
• Last Updated: December 22, 2023
• Results First Posted: March 30, 2015

Record last verified: 2023-12

Locations

US (7)