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

Mayo Clinic

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Treatments

Drug: prasterone

Drug: clarithromycin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00006219

P30CA015083 (U.S. NIH Grant/Contract)

CDR0000068084

979202 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: