Celecoxib in Preventing Multiple Myeloma in Patients With Monoclonal Gammopathy or Smoldering Myeloma

PRIMARY OJBECTIVES:

I. Determine the efficacy of celecoxib vs placebo in reducing serum levels of M-component in patients with monoclonal gammopathy of undetermined significance or smoldering myeloma.

SECONDARY OBJECTIVES:

I. Determine the effects of this drug on secondary biomarkers as surrogate endpoints in these patients.

OUTLINE:

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and type of monoclonal gammopathy (monoclonal gammopathy of undetermined significance vs smoldering myeloma). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive celecoxib orally (PO) twice daily (BID) for 6 months in the absence of unacceptable toxicity or progression to malignancy.

ARM II: Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.

After completion of study treatment, patients are followed at 1, 6, and 12 months.

Criteria:

• M-protein >= 30 g/L
• No clinical evidence of chronic infectious or inflammatory disease
• No present evidence of active malignancy (nonmelanoma skin cancer or cervical intraepithelial neoplasia allowed)
• No hypersensitivity (e.g., asthma, urticaria, or acute rhinitis induced by NSAIDs) to aspirin or other NSAIDs
• No hypersensitivity to sulfonamides
• No uncontrolled diabetes
• No history of diabetic retinopathy
• No condition that would preclude study participation
• No condition that would preclude the use of NSAIDs
• New or preexisting diagnosis of 1 of the following for at least 2 months:
• Monoclonal gammopathy of undetermined significance as defined by the following criteria:
• M-protein =< 30 g/L
• Bone marrow clonal plasma cells < 10% and low level of plasma cell infiltration in a trephine biopsy (if done)
• Smoldering myeloma as defined by at least 1 of the following criteria:
• Bone marrow clonal plasma cells >= 10%
• No related organ or tissue impairment (i.e., end organ damage) or symptoms
• Asymptomatic patients with =< 3 lytic lesions (without other organ damage) attributable to plasma cell dyscrasia allowed
• No condition associated with a secondary monoclonal gammopathy
• IgG, IgA, or light chain M-component >= 1.0 g/dL for at least 2 consecutive lab readings taken at least 4 weeks apart
• No anemia
• No hepatic insufficiency
• AST or ALT < 1.5 times upper limit of normal (ULN)
• Bilirubin =< 1.5 times ULN
• Creatinine =< 1.8 mg/dL
• No hypercalcemia
• No renal insufficiency
• No uncontrolled congestive heart failure
• No history of cerebrovascular or cardiovascular accident
• No history of gastrointestinal hemorrhage
• No active or suspected peptic ulcer disease
• Previously treated H. pylori infection allowed
• More than 12 months since limited chemotherapy
• More than 28 days since prior chronic or frequent use of glucocorticoids (> 5 mg of prednisone or equivalent per day)
• More than 28 days since prior chronic or frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) (> 100 mg of aspirin per day)
• More than 28 days since prior bisphosphonate therapy
• More than 28 days since prior investigational agents
• Concurrent low-dose aspirin ( =< 100 mg/day) allowed
• No evidence of other B-cell proliferative disorders (e.g., multiple myeloma, Waldenstrom's macroglobulinemia, primary amyloidosis, or lymphoproliferative disease)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• AND/OR
• ECOG 0-1 or Zubrod 0-1