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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00099047
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

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

Detailed Description

PRIMARY OJBECTIVES:

1. 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:

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Biologic and Clinical Role of COX-2 Inhibitor (Celecoxib)in the Management of MGUS and Smoldering Myeloma
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

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.	Drug: celecoxib; Given PO; Other Names: Celebrex ; 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: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Matt Kalaycio, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00099047
• Other Study ID Numbers: NCI-2009-00866; NCI-2009-00866; CDR0000393514; UARK-18697; MAYO-206904; CCF-IRB-7029; N01-CN-25140; N01CN25140
• First Posted: Dec 9, 2004
• Last Update Posted: Dec 30, 2016
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Celecoxib

Study Results

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 Detail	There were no significant events or approaches utilized following enrollment but prior to group assignment.

Arm/Group Title	Arm I (Celecoxib)	Arm II (Placebo)
Arm/Group Description	Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.	Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.
Period Title: Overall Study
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Celecoxib)	Arm II (Placebo)	Total
Arm/Group Description	Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.	Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.	Total of all reporting groups
Overall Participants	11	12	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 72.7%	9 75%	17 73.9%
>=65 years	3 27.3%	3 25%	6 26.1%
Gender (Count of Participants)
Female	5 45.5%	4 33.3%	9 39.1%
Male	6 54.5%	8 66.7%	14 60.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	0 0%	1 4.3%
Not Hispanic or Latino	10 90.9%	12 100%	22 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 8.3%	1 4.3%
White	11 100%	11 91.7%	22 95.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	12 100%	23 100%
serum monoclonal protein >1g/dL (participants) [Number]
Number [participants]	11 100%	12 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Changes in M-protein Levels
Description	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

Outcome Measure Data

Analysis Population Description

One patient on the celecoxib arm was considered inevaluable and not included in this participants analyzed.

Arm/Group Title	Arm I (Celecoxib)	Arm II (Placebo)
Arm/Group Description	Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.	Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.
Measure Participants	10	12
Median (Standard Deviation) [g/dL]	1.65 (0.36)	2.24 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Celecoxib), Arm II (Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.23
	Comments
	Method	SAS version 8
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: .05
	Estimation Comments	36 evaluable patients randomized 1:1 to each treatment was planned in order to have >77% power to detect differences in above parameters equal to or greater than one standard deviation, based on a 2-sided Wilcoxon rank-sum test with .05 Type I error.

Adverse Events

Arm/Group Title	Arm I (Celecoxib)		Arm II (Placebo)
Arm/Group Description	Patients receive celecoxib PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.		Patients receive placebo PO BID for 6 months in the absence of unacceptable toxicity or progression to malignancy.
All Cause Mortality
	Arm I (Celecoxib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Celecoxib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Celecoxib)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)		8/12 (66.7%)
Gastrointestinal disorders
Diarrhea	2/11 (18.2%)	2	1/12 (8.3%)	1
Constipation	2/11 (18.2%)	2	0/12 (0%)	0
General disorders
Fatigue	1/11 (9.1%)	1	2/12 (16.7%)	2
Infections and infestations
Upper Respiratory	1/11 (9.1%)	1	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/11 (9.1%)	1	1/12 (8.3%)	1
Exremity Limb Pain	0/11 (0%)	0	2/12 (16.7%)	5
Neck Pain	2/11 (18.2%)	2	1/12 (8.3%)	1
Pain NOS	0/11 (0%)	0	2/12 (16.7%)	2
Nervous system disorders
headache	2/11 (18.2%)	2	4/12 (33.3%)	4
Dizziness	1/11 (9.1%)	1	1/12 (8.3%)	1
Neuorpathy	2/11 (18.2%)	2	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus/Itching	2/11 (18.2%)	2	1/12 (8.3%)	1

Limitations/Caveats

No overall limitations or caveats for this trial.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.