Trial Information

Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma

OBJECTIVES:

- Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and
cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon
alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.

- Determine the response rate and progression-free and overall survival of patients
treated with this regimen.

- Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in
patients who are not in complete remission (CR) 6 months after the second course of
high-dose chemotherapy.

- Determine whether administration of thalidomide can increase the CR rate in patients
who are not in CR 6 months after the second course of high-dose chemotherapy and
determine its effect on progression-free and overall survival of these patients.

- Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the
pharmacokinetics with the toxic effects of these drugs and outcome in these patients.

- Determine the effect of thalidomide on microvascular density of bone marrow and
correlate these possible effects with outcome in these patients.

- Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization
in baseline and post treatment bone marrow and blood specimens and correlate the
presence/persistence of these features with treatment outcome in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF)
subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral
blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.

Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is
administered IV or SC daily beginning on day 1 and continuing until blood counts recover.
Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days
-7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day
0 and G-CSF is administered IV or SC daily until blood counts recover.

Patients with responding or stable disease after chemotherapy receive maintenance therapy
with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy.
Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive
pamidronate IV every 4 weeks until disease progression. Patients who are not in complete
remission (CR) 6 months after completing the second course of chemotherapy receive oral
thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically
thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within
approximately 2.5 years.