Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Light Chain Amyloidosis
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib, cyclophosphamide, and dexamethasone together works in treating patients with primary systemic light chain amyloidosis.
Primary Systemic Amyloidosis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Light Chain Amyloidosis|
- Number of Participants With a Confirmed Hematologic Response [ Time Frame: Duration of treatment (up to 12 cycles/months) ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations during treatment.
Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.
Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
- Number of Participants With Treatment Related Adverse Events. [ Time Frame: Duration on treatment (up to 12 cycles/months) ] [ Designated as safety issue: Yes ]
Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE.
Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE
Adverse events will be assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0.
- Number of Participants With an Organ Response. [ Time Frame: Duration on treatment (up to 12 cycles/months) ] [ Designated as safety issue: No ]The number of patients that acheived a response in an affected organ.
- Overall Survival [ Time Frame: Duration of Study (up to 5 years) ] [ Designated as safety issue: No ]Survival time is defined as the time from registration to death due to any cause.
- Time to Disease Progression [ Time Frame: Duration of Study (up to 5 years) ] [ Designated as safety issue: No ]Time to disease progression is defined as the time from registration to the earliest date of documented disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death
- Duration of Response [ Time Frame: Duration of Study (up to 5 years) ] [ Designated as safety issue: No ]Duration of response will be calculated from the date of first evidence of response until the date of progression in the subset of patients with confirmed hematologic responses.
|Study Start Date:||March 2010|
|Study Completion Date:||June 2012|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Bortezomib IV on days 1, 8, and 15, oral cyclophosphamide and oral dexamethasone once daily on days 1, 8, 15, and 22.
1.3 mg/m^2, by IV on days 1, 8 and 15 every 28 days
Other Names:Drug: cyclophosphamide
300 mg/m^2, orally, on days 1, 8, 15 & 22 every 28 days.
Other Names:Drug: dexamethasone
40 mg, orally, on days 1, 8, 15 & 22 every 28 days
I. To assess the confirmed hematologic response rate of the combination of bortezomib, cyclophosphamide and dexamethasone in patients with primary systemic amyloidosis.
I. Organ response rate of the bortezomib, cyclophosphamide and dexamethasone combination.
II. Severity and frequency of adverse events associated with bortezomib, cyclophosphamide and dexamethasone treatment in patients with primary systemic amyloidosis.
III. Time to progression.
OUTLINE: Patients receive bortezomib IV on days 1, 8, and 15 and oral cyclophosphamide and oral dexamethasone once daily on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for 2 years.