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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: celecoxib; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Matt Kalaycio, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: December 8, 2004
• First Submitted That Met QC Criteria: December 8, 2004
• First Posted (Estimate): December 9, 2004

Study Record Updates

• Last Update Posted (Estimate): December 30, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: NCI-2009-00866 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000393514; UARK-18697; MAYO-206904; CCF-IRB-7029 (Other Identifier: Cleveland Clinic Foundation); N01-CN-25140 (Other Identifier: DCP); N01CN25140 (Other Identifier: US NIH Grant/Contract Award Number)