Bortezomib in Treating Patients With Newly Diagnosed High-Risk Stage III Multiple Myeloma

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.

Official Title

Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Type

Interventional

Study Design

Treatment, Open Label

Further Details

OBJECTIVES:Primary

• Determine the response rate in patients with newly diagnosed high-risk stage III multiple myeloma treated with bortezomib induction therapy.

Secondary

• 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.

Study Start

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])

Hematopoietic

• Platelet count >= 20,000/mm³ (transfusion allowed)
• Hemoglobin >= 7.0 g/dL (transfusion allowed)
• Absolute neutrophil count >= 500/mm³ (without growth factor support)

Hepatic

• Bilirubin =< 1.5 times upper limit of normal (ULN)
• AST =< 2.5 times ULN
• Alkaline phosphatase =< 2.5 times ULN

Renal

• Creatinine clearance >= 20 mL/min

Cardiovascular

• 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

Other

• 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

Chemotherapy

• No prior chemotherapy for multiple myeloma
• No concurrent chemotherapy

Endocrine therapy

• Concurrent corticosteroids allowed for treatment of chronic disorders other than multiple myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)

Radiotherapy

• 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

Other

• Prior or concurrent bisphosphonates allowed
• No other concurrent antineoplastic therapy for multiple myeloma

Total Enrolment

44

Contact Details

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.