Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

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

Summary: 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: 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.

Eligibility: 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

Relevance to patient case: not relevant