Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
RATIONALE: 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide and dexamethasone together with bortezomib may kill more cancer cells.
PURPOSE: This phase II trial is studying giving cyclophosphamide and dexamethasone together with bortezomib to see how well it works in treating patients with newly diagnosed multiple myeloma.
Multiple Myeloma and Plasma Cell Neoplasm
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Cyclophosphamide, Bortezomib and Dexamethasone (CYBOR-D) in Patients With Newly Diagnosed Active Multiple Myeloma|
- Number of Participants Who Achieved a Confirmed Responses Defined as a Complete Response (CR), Near CR or Very Good Partial Response (VGPR) After the First 4 Months of Treatment [ Time Frame: After 4 months of treatment ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations during the first 4 months of 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.
near Complete Response (nCR): Patients who meet all criteria for CR except a positive immunofixation will be classified as nCR.
Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow.
- Progression Free Survival (PFS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
PFS was defined as the time from registration to progression or death due to any cause.
Progression was defined as any one or more of the following:
An increase of 25% from lowest confirmed response in:
- Serum M-component (absolute increase >= 0.5g/dl)
- Urine M-component (absolute increase >= 200mg/24hour
- Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
- Bone marrow plasma cell percentage (absolute increase of >=10%)
- Definite development of new bone lesion or soft tissue plasmacytomas
- Overall Survival (OS) [ Time Frame: From date of registration until death (up to 5 years) ] [ Designated as safety issue: No ]OS was defined as the time from registration to death of any cause.
- Number of Participants Who Responded to Treatment (Complete Response,CR; Near Complete Response, nCR; Very Good Partial Response, VGPR; or Partial Response, PR) After 4 Cycles [ Time Frame: 4 cycles ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations after 8 months of treatment.
CR, nCR and VGPR as defined in the primary outcome.
Partial Response(PR): >=50% reduction in serum M-component and/or
Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
- Duration of Response [ Time Frame: Duration of study (up to 12 cycles) ] [ Designated as safety issue: No ]Duration of response was calculated from the documentation (date) of first response (CR, nCR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded.
- Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 8 Cycles [ Time Frame: After 8 cycles of treatment ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations after 8 cycles of treatment.
Criteria for CR, nCR, VGPR and PR are defined in prior outcomes.
- Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 12 Cycles [ Time Frame: After 12 cycles of treatment ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations after 12 cycles of treatment.
Criteria for CR, nCR, VGPR and PR are defined in prior outcomes.
- Number of Participants With Severe Adverse Events [ Time Frame: Every cycle during treatment (up to 12 cycles) ] [ Designated as safety issue: Yes ]Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
- Participants Who Successfully Completed Collection of Peripheral Blood Stem Cells for Transplant [ Time Frame: After 4 cycles of treatment ] [ Designated as safety issue: No ]Evaluation of the ability to successfully collect peripheral blood stem cells following four months (cycles) of combination therapy.
|Study Start Date:||December 2006|
|Study Completion Date:||November 2010|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
First 33 patients: 1.3 mg/m^2 IV Days 1, 4, 8 & 11
Remaining 30 patients: 1.5 mg/m^2 IV Days 1, 8, 15 & 22
First 33 patients: 40 mg PO Days 1-4, 9-12, 17-20
Remaining 30 patients: 40 mg PO Days 1-4, 9-12, 17-20 for cycles 1-2; Days 1, 8, 15, 22 for cycle 3+2 for cycle 3 and beyond
* To evaluate the response rate (complete response [CR], near CR [nCR], and very good partial response) in patients with newly diagnosed multiple myeloma treated with bortezomib in combination with cyclophosphamide and dexamethasone .
- Determine the overall response rate (partial response, PR, or better) in these patients after 4, 8, and 12 courses of this regimen.
- Determine the duration of progression-free and overall survival of patients treated with this regimen.
- To evaluate the toxicity of this regimen in these patients.
- To evaluate the ability to successfully collect peripheral blood stem cells from these patients after 4 months of this regimen.
- To evaluate the CR or nCR rate in these patients after 8 and 12 courses of this regimen.
OUTLINE: This is a multicenter study.
Patients receive oral cyclophosphamide on days 1, 8, 15, and 22; bortezomib IV on days 1, 4, 8 , and 11 OR days 1, 8, 15 and 22; and dexamethasone on days 1-4, 9-12, and 17-20 in courses 1 and 2 and days 1, 18, 15, and 22 in all subsequent courses. Courses repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259-5499|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2N9|
|Principal Investigator:||A. Keith Stewart, M.B., Ch.B.||Mayo Clinic|