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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: clarithromycin
* Drug: prasterone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: clarithromycin|nan|
|Drug: prasterone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma