Chemoprevention Therapy in Treating Patients at High Risk of Developing Multiple Myeloma

Official Title: “A Phase II Clinical Trial of Dehydroepiandrosterone and Biaxin in Monoclonal Gammopathy of Undetermined and Borderline Significance”

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Dehydroepiandrosterone and clarithromycin may be effective in preventing multiple myeloma.

PURPOSE: Randomized phase II trial to compare the effectiveness of dehydroepiandrosterone with that of clarithromycin in treating patients who may be at a high risk of developing multiple myeloma.

OBJECTIVES: - Determine whether dehydroepiandrosterone (DHEA) or clarithromycin causes a significant reduction in bone marrow plasmacytosis, serum and/or urine M protein or Bence Jones protein, and surrogate endpoint biomarkers in patients with monoclonal gammopathy of undetermined or borderline significance. - Determine whether differences in interleukin-1-beta (IL-1-beta) expression and IL-1-beta dependent biomarkers (adhesion molecule expression and serum interleukin-6 levels) are useful surrogate endpoint biomarkers in these patients. - Determine whether differences in ploidy, proliferative index, nuclear pleomorphism index, circulating monoclonal plasma cells, Th1/Th2 ratios, serum s-interleukin-6R (SIL-6R) levels, interleukin-6 and SIL-6R expression, or plasma cell apoptosis assay are useful surrogate endpoint biomarkers in these patients. - Determine the effects of these treatment regimens on the quality of life of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to disease (monoclonal gammopathy of undetermined significance vs monoclonal gammopathy of borderline significance) and monoclonal protein abnormality (IgG vs IgA). Patients are randomized to 1 of 4 treatment arms. - Arm I: Patients receive oral dehydroepiandrosterone (DHEA) once daily. - Arm II: Patients receive oral clarithromycin once or twice daily. - Arm III: Patients receive oral placebo once daily. - Arm IV: Patients receive oral placebo twice daily. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 6 months, 12 months, and then at disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 1.5 years.

PROJECTED ACCRUAL: A total of 75 patients (25 per treatment arms I and II and 25 between arms III and IV) will be accrued for this study within 2.5 years.

Intervention(s) in this Clinical Trial

• Drug: clarithromycin
• Drug: prasterone

DISEASE CHARACTERISTICS:

• New or prior diagnosis of 1 of the following:
• Monoclonal gammopathy of undetermined significance
• Bone marrow plasma cells of less than 10%
• Monoclonal gammopathy of borderline significance
• Bone marrow plasma cells of 10-30%
• Serum IgG or IgA at least 1.5 g/dL
• Bone marrow plasmacytosis no greater than 30%
• No multiple myeloma, amyloidosis, or B-cell neoplasm
• No evidence of bone lesions
• Prostate-specific antigen less than 4 ng/mL

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless history of Gilbert's disease)
• AST and ALT no greater than 1.5 times ULN (unless history of Gilbert's disease)

Renal:

• Creatinine no greater than 1.8 mg/dL

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No prior thromboembolic event within the past 5 years

Other:

• No prostate cancer or clinically significant benign prostatic hypertrophy
• No prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No malignancy suspected on mammogram
• No hypersensitivity to DHEA, clarithromycin, or any macrolide antibiotic (e.g., erythromycin)
• No insulin-dependent diabetes
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier method of contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• At least 30 days since prior DHEA or other steroids that may affect M protein

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 30 days since prior clarithromycin
• At least 30 days since any other prior agents that may affect M protein
• No concurrent cisapride, terfenadine, pimozide, astemizole, or loratadine

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Mayo Clinic Other

Overall Clinical Trial Officials and Contacts

John A. Lust, MD, PhD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00006219

Study ID Number: CDR0000068084

ClinicalTrials.gov Identifier: NCT00006219

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database