• Compare complete response and near complete response rate after completion of the first transplant [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the complete response (CR) and near-CR rates in patients with stage II or III multiple myeloma treated with induction therapy comprising two different doses of high-dose melphalan and amifostine followed by a single autologous or syngeneic peripheral blood stem cell transplantation (PBSCT).

Secondary

• Compare the toxic effects of these regimens in these patients.
• Determine the CR and near-CR rates in patients who fail to achieve a CR or near-CR after a single autologous or syngeneic PBSCT and subsequently receive a second course of induction therapy comprising high-dose melphalan and amifostine followed by a second autologous or syngeneic PBSCT.
• Compare the time to progression in patients treated with these regimens followed by maintenance therapy comprising clarithromycin, thalidomide, and dexamethasone.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to pre-transplantation response (< a partial response [PR] vs > a PR), pre-transplantation serum beta-2 microglobulin level (< 5 mg/dL vs > 5 mg/dL), and the presence of deletion on chromosome 13 by fluorescence in situ hybridization (yes vs no).

• Induction therapy: Patients are randomized to 1 of 2 treatment arms.

  • Arm I (high-dose melphalan and amifostine): Patients receive amifostine IV over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day -2.
  • Arm II (higher-dose melphalan and amifostine): Patients receive amifostine as in arm I and melphalan as in arm I but at a higher dose.
• Autologous or syngeneic peripheral blood stem cell transplantation (PBSCT): At least 20 hours after completion of melphalan, all patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a complete response (CR) or near-CR proceed to maintenance therapy. Patients who do not achieve a CR or near-CR undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT. Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease proceed to maintenance therapy.

• Maintenance therapy: Beginning 90-120 days after first or second PBSCT, patients receive oral clarithromycin twice daily and oral thalidomide once daily for 1 year. Patients also receive oral dexamethasone once weekly for 1 year followed by a taper for 8 weeks. Treatment with thalidomide alone then continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 130 patients will be accrued for this study.