Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Smoldering Multiple Myeloma
Conditions
Brief summary
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
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.
Interventions
DRUGcelecoxib
Given PO
DRUGplacebo
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in M-protein Levels | Baseline and 6 months | 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. |
Countries
United States
Participant flow
Recruitment details
23 asymptomatic adult patients with a serum monoclonal protein \>1g/dL from Cleveland Clinic, Mayo Clinic, or University of Arkansas Medical Center were randomized between August 2005 and April 2008
Pre-assignment details
There were no significant events or approaches utilized following enrollment but prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Celecoxib) Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy. | 11 |
| Arm II (Placebo) Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy. | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Arm II (Placebo) | Arm I (Celecoxib) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 10 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 4 Participants | 5 Participants | 9 Participants |
| Gender Male | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| serum monoclonal protein >1g/dL | 12 participants | 11 participants | 23 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 11 | 8 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline and 6 months
Population: One patient on the celecoxib arm was considered inevaluable and not included in this participants analyzed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm I (Celecoxib) | Changes in M-protein Levels | 1.65 g/dL | Standard Deviation 0.36 |
| Arm II (Placebo) | Changes in M-protein Levels | 2.24 g/dL | Standard Deviation 0.36 |
p-value: 0.23SAS version 8