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

Study Overview
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Brief Summary
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This randomized phase II trial studies how well celecoxib works in preventing multiple myeloma in patients with monoclonal gammopathy or smoldering myeloma. Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be effective in preventing multiple myeloma.

Detailed Description
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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.

Official Title
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Biologic and Clinical Role of COX-2 Inhibitor (Celecoxib)in the Management of MGUS and Smoldering Myeloma

Conditions
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Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Smoldering Multiple Myeloma

Intervention / Treatment
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* Drug: celecoxib
* Drug: placebo
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (celecoxib)<br>Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy. | Drug: celecoxib<br>* Given PO<br>* Other names: Celebrex;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy. | Drug: placebo<br>* Given PO<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in M-protein Levels | For a given biomarker (or a suitable transformation of it, e.g. log transform) t-tests and Wilcoxon tests (2-sample t-test and Wilcoxon rank sum test for between treatment comparisons, and paired 1-sample t-test and Wilcoxon signed rank test for within treatment comparisons) will be used to detect statistically significant differences between (or within) treatments. | Baseline and 6 months |