Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma

Launched by FRED HUTCHINSON CANCER CENTER · Feb 20, 2007

Keywords

ClinConnect Summary

OBJECTIVES:

Primary

* Determine the response rate in patients with newly diagnosed, previously untreated multiple myeloma treated with bortezomib, cyclophosphamide, dexamethasone, and thalidomide.

Secondary

* Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive bortezomib IV on days 1, 4, 8, and 11; cyclophosphamide IV on days 1 and 8 of courses 1-3; oral thalidomide once daily on days 1-21 beginning in course 4; and dexamethasone IV or orally once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatm...

Gender

ALL

Eligibility criteria

• DISEASE CHARACTERISTICS:
• * Diagnosis of multiple myeloma meeting 1 of the following criteria:
• * Monoclonal immunoglobulin spike on serum electrophoresis (IgG \> 3.5 g/dL or IgA \> 2.0 g/dL) and kappa or lambda light chain excretion \> 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:
• • Bone marrow plasmacytosis (10-30% plasma cells)
• • Lytic bone lesions
• * Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:
• • Lytic bone lesions
• • IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• * Bone marrow plasmacytosis (\> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:
• • Monoclonal immunoglobulin of lesser magnitude present
• • Lytic bone lesions
• • IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL
• • FreeLite testing abnormal and kappa:lambda light chain ratio abnormal
• • Symptomatic disease requiring treatment
• • Documented related organ or tissue involvement, if present
• * Measurable disease, defined as 1 of the following:
• • Monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/day
• • Abnormal FreeLite testing (for nonsecretors)
• * Patients with nonsecretory disease must meet either of the following criteria for measurability:
• • Has measurable protein by FreeLite testing
• • Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow
• • Newly diagnosed, previously untreated disease
• • No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\], and skin changes)
• • No plasma cell leukemia
• PATIENT CHARACTERISTICS:
• • Karnofsky performance status 50-100%
• • Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ if bone marrow is extensively infiltrated)
• • Extensive infiltration is defined as \> 50% myeloma cells or plasma cells
• • Hemoglobin ≥ 8.5 g/dL
• • Absolute neutrophil count ≥ 1,500/mm³
• • AST and ALT ≤ 2 times upper limit of normal (ULN)
• • Bilirubin ≤ 1.5 times ULN (unless clearly related to the disease)
• • Creatinine clearance ≥ 20 mL/min
• • Not pregnant or nursing
• • Negative pregnancy test
• • Fertile patients must use 2 methods of effective contraception ≥ 4 weeks prior to beginning treatment, during, and for ≥ 4 weeks after completion of study treatment
• • No impaired kidney function requiring dialysis
• • No uncontrolled infection
• • No HIV positivity
• • No known active hepatitis B or C
• * No cardiovascular disease including, but not limited to, any of the following:
• • Myocardial infarction within the past 6 months
• • New York Heart Association class II-IV heart failure
• • Uncontrolled angina
• • Severe uncontrolled ventricular arrhythmias
• • Clinically significant pericardial disease
• • Acute ischemic or active conduction system abnormalities by EKG
• • No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide
• • No second malignancy requiring concurrent treatment
• • No other serious medical or psychiatric illness that would preclude study compliance
• • No peripheral neuropathy ≥ grade 1
• PRIOR CONCURRENT THERAPY:
• • No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma
• • Drugs given to prevent onset of myeloma allowed
• • Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed
• • Prior local radiotherapy with or without a brief exposure to steroids allowed
• • More than 4 weeks since prior and no concurrent radiotherapy
• • Spot radiotherapy to ≤ 3 vertebrae allowed
• • No concurrent steroids at \> 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)
• • No other concurrent chemotherapy or investigational agents
• • Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment