Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma

PRIMARY OBJECTIVES:

I. To determine the overall response rate (ORR) and toxicity rate of therapy with weekly
bortezomib combined with oral metronomic cyclophosphamide and low-dose dexamethasone.

SECONDARY OBJECTIVES:

I. To determine overall survival. II. To describe the association between disease status,
treatment response, treatment toxicity, quality of life, functional status, risk for
development of frailty, and inflammatory cytokine levels.

OUTLINE:

Patients receive bortezomib subcutaneously (SC) or intravenously (IV) over 3-5 seconds on
days 1, 8, and 15; cyclophosphamide orally (PO) once daily (QD) on days 1-21; and
dexamethasone PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 8 courses
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 3
months.

Inclusion Criteria:

- Patients must have a confirmed diagnosis of symptomatic myeloma in accordance with
International Myeloma Working group (IMWG) criteria

- Bone marrow plasmacytosis with > 10% plasma cells or sheets of plasma cells or
biopsy proven plasmacytoma

- Symptomatic disease, i.e., end-organ damage due to multiple myeloma (MM)
including at least one of the following: anemia, hypercalcemia, bone disease
(lytic bone lesions or pathologic fracture), or renal dysfunction

- Absolute neutrophil count (ANC) >= 1000 cells/mm^3 (without use of growth factors)

- Platelets >= 50,000 cells/mm^3

- Direct bilirubin =< 1.5 X upper limit of normal (ULN); elevated bilirubin is
permissible if patient has a known history of elevated bilirubin due to Gilbert's or
if elevated bilirubin is due to hemolysis

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5
X ULN

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document

Exclusion Criteria:

- Prior treatment with > 1 cycle of any plasma cell myeloma (PCM) induction regimen
(maximum 6 weeks of prior treatment)

- Prior radiation therapy is allowed

- Prior treatment for other cancers is allowed as long as patient meets criteria
for adequate hematopoietic and organ function and is not actively on
chemotherapy for another cancer

- Grade >= 2 peripheral neuropathy

- Second malignancy currently undergoing chemotherapy or radiotherapy; hormonal therapy
for breast or prostate cancer is allowed

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bortezomib, cyclophosphamide, dexamethasone or other agents used in
this study

- Patients with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements