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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00099047
First received: December 8, 2004
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
Smoldering Multiple Myeloma
Drug: celecoxib
Drug: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Biologic and Clinical Role of COX-2 Inhibitor (Celecoxib)in the Management of MGUS and Smoldering Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Changes in M-protein levels [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Changes in serum IL-6 levels [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in serum IL-6 receptor levels [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in serum beta-2 microglobulin levels [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in CD4+/CD8+ ratio [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in IL-1 beta levels [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in COX-2 staining [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in peripheral blood labeling index [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 36
Study Start Date: November 2004
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (celecoxib)
Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.
Drug: celecoxib
Given PO
Other Names:
  • Celebrex
  • SC-58635
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.
Drug: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099047

Locations
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Investigators
Principal Investigator: Rachid Baz The Cleveland Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00099047     History of Changes
Other Study ID Numbers: NCI-2009-00866, CCF-IRB-7029, CDR0000393514, UARK-18697, MAYO-206904, N01CN25140
Study First Received: December 8, 2004
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Multiple Myeloma
Neoplasms, Plasma Cell
Hypergammaglobulinemia
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014