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


Multiple Myeloma and Plasma Cell Neoplasm

Study Type


Study Design

Treatment, Open Label

Further Details


  • 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.

Study Start

Eligibility & Criteria

  • Ages Eligible for Study: 18 Years and above
  • Genders Eligible for Study: Both


  • 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


  • 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


  • No prior biologic therapy for multiple myeloma
  • No concurrent biologic therapy
  • No concurrent pegfilgrastim


  • 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)


  • 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

Total Enrolment


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.