RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with newly diagnosed high-risk stage III multiple myeloma.
Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma
Multiple Myeloma and Plasma Cell Neoplasm
Treatment, Open Label
- Determine the response rate in patients with newly diagnosed high-risk stage III multiple myeloma treated with bortezomib induction therapy.
- Determine the progression-free survival of patients treated with this drug.
- Determine the response rate and duration of second response in patients who relapse or progress while on maintenance therapy and subsequently receive reinduction therapy with this drug.
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression must complete at least 2 courses of induction therapy. Patients who achieve complete remission receive 2 additional courses, but no more than 8 courses total, and then proceed to maintenance therapy.
- Maintenance therapy: Patients receive bortezomib IV over 3-5 seconds on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may return to induction therapy (reinduction therapy).
- Reinduction therapy: Patients receive bortezomib as in induction therapy. Courses repeat every 3 weeks until second disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 4 years from study entry.
Eligibility & Criteria
- Ages Eligible for Study: 18 Years and above
- Genders Eligible for Study: Both
Inclusion Criteria:DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma meeting the following criteria:
- Symptomatic disease diagnosed within the past 30 days
- Measurable or evaluable disease meeting at least 1 of the following criteria:
- Serum monoclonal protein >= 1 g/dL (measurable disease)
- Monoclonal light chain in urine protein electrophoresis >= 200 mg/24-hour urine collection (measurable disease)
- Bone marrow plasmacytosis >= 30% (evaluable disease)
- High-risk disease, defined by >= 1 of the following criteria:
- Beta 2-microglobulin >= 5.5 micrograms/mL
- Plasma cell labeling index >= 1%
- Deletion of chromosome 13 by cytogenetic analysis
PATIENT CHARACTERISTICS:Performance status
- ECOG 0-2 (ECOG 3 allowed if secondary to acute bone event [i.e., fracture])
- Platelet count >= 20,000/mm3 (transfusion allowed)
- Hemoglobin >= 7.0 g/dL (transfusion allowed)
- Absolute neutrophil count >= 500/mm3 (without growth factor support)
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- AST =< 2.5 times ULN
- Alkaline phosphatase =< 2.5 times ULN
- Creatinine clearance >= 20 mL/min
- No myocardial infarction within the past 6 months
- No New York Heart Association class III or IV heart failure
- No uncontrolled angina
- No acute ischemia by EKG
- No severe uncontrolled ventricular arrhythmias
- No active conduction system abnormalities by EKG
- No cardiac amyloidosis
- No poorly controlled hypertension
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reaction attributable to compounds containing boron or mannitol
- No greater than grade 1 peripheral neuropathy
- No other serious medical or psychiatric illness that would preclude study completion
PRIOR CONCURRENT THERAPY:Biologic therapy
- No prior biologic therapy for multiple myeloma
- No concurrent biologic therapy
- No concurrent pegfilgrastim
- No prior chemotherapy for multiple myeloma
- No concurrent chemotherapy
- Concurrent corticosteroids allowed for treatment of chronic disorders other than multiple myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)
- No prior radiotherapy for multiple myeloma
- At least 4 weeks since prior radiotherapy for plasmacytoma (e.g., solitary plasmacytoma)
- No concurrent radiotherapy
- Concurrent localized radiotherapy allowed upon approval by study chair
- Prior or concurrent bisphosphonates allowed
- No other concurrent antineoplastic therapy for multiple myeloma
Westmead Hospital, Westmead, New South Wales, 2145, Australia More information available from The National Cancer InstituteResults Published in:
- Dispenzieri A, Zhang L, Fonseca R, et al.: Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02). [Abstract] Blood 108 (11): A-3527, 2006.