Trial Information

Autologous Transplantation for Multiple Myeloma: A Research Study of Multiple Myeloma Using Chemotherapy Plus Growth Factor Primed Peripheral Blood Stem Cells Followed by Autologous Transplantation and Post-Transplant Immunotherapy

OBJECTIVES:

- Compare disease control and extended survival in patients with multiple myeloma when
treated with either filgrastim (G-CSF) or sargramostim (GM-CSF) plus high-dose
chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation
followed by interferon alfa.

- Determine whether these priming treatments induce sufficient mobilization of
circulating PBSC to allow their collection by leukapheresis for subsequent use in
autologous transplantation in these patients.

- Determine whether these treatments induce complete response in conjunction with rapid
hematopoietic recovery and modest transplant-associated morbidity and mortality in this
patient population.

- Determine whether interferon alfa, given as maintenance immunostimulatory therapy for
patients achieving significant cytoreduction post transplantation, can prevent or delay
malignant relapse in these patients.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

- Arm I: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day
1, mitoxantrone IV over 1 hour daily on days 1-2, and dexamethasone IV every 12 hours
beginning on day 1 for a total of 4 doses. Patients also receive sargramostim (GM-CSF)
IV over 2 hours or subcutaneously (SC) daily beginning 48 hours after the last dose of
mitoxantrone and continuing until completion of leukapheresis. Peripheral blood stem
cells (PBSC) are collected daily on days 11-13 after neutrophil recovery.

- Arm II: In the priming phase, patients receive the same treatment as in arm I except
these patients receive filgrastim (G-CSF) IV over 15 minutes or SC in place of GM-CSF.

In the transplant phase, patients who have not received prior radiotherapy receive
cyclophosphamide IV over 2 hours daily on days -6 and -5 and total body irradiation twice
daily on days -3 through -1. Autologous PBSC are reinfused on day 0. Patients also receive
GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes daily beginning on day 0 and
continuing until day 28 or until blood counts recover.

Patients who have received prior radiotherapy receive cyclophosphamide IV over 2 hours daily
on days -6 through -3, carmustine IV over 1 hour on day -6, and etoposide IV over 4 hours
every 12 hours for a total of 6 doses on days -6 through -4. Autologous PBSC are reinfused
on day 0. Patients also receive GM-CSF IV over 2 hours daily and G-CSF IV over 15 minutes
daily beginning on day 0 and continuing until day 28 or until blood counts recover.

All patients then receive interferon alfa SC 3 times weekly starting on day 28 and
continuing until relapse or disease progression.

Patients may also undergo radiotherapy 5 days a week for 2 weeks for residual bony lesions
measuring greater than 2 cm.

Patients are followed at days 28 and 100, and at 6, 9, 12, 18, 24, 30, and 36 months.

PROJECTED ACCRUAL: A total of 25-35 patients will be accrued for this study within 2-3
years.