Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI ECOG-E2A02 E2A02, NCT00075881

Objectives

Primary

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

Secondary

1. Determine the progression-free survival of patients treated with this drug.
2. 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.

Entry 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 μg/mL
  • Plasma cell labeling index ≥ 1%
  • Deletion of chromosome 13 by cytogenetic analysis

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

Surgery

• Not specified

Other

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2 (ECOG 3 allowed if secondary to acute bone event [i.e., fracture])

Life expectancy

• Not specified

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

Expected Enrollment

A total of 44 patients will be accrued for this study within 7 months.

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.

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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Angela Dispenzieri, MD, Protocol chair		Ph: 507-284-2511

Registry Information
Official Title		Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma
Trial Start Date		2004-01-16
Registered in ClinicalTrials.gov		NCT00075881
Date Submitted to PDQ		2003-12-09
Information Last Verified		2005-11-30
NCI Grant/Contract Number		U10-CA21115

Back to Top