Trial Information

Autologous Followed By Non-Myeloablative Allogeneic Transplant For Multiple Myeloma

OBJECTIVES:

- Determine whether autologous peripheral blood stem cell transplantation (PBSCT)
followed by non-myeloablative allogeneic PBSCT is associated with no more than 20%
treatment-related mortality rates at 6 months in patients with multiple myeloma.

- Determine the response rate of patients treated with this regimen.

- Determine the percent donor chimerism in patients treated with this regimen.

- Determine the rate of graft-vs-host disease in patients treated with this regimen.

- Determine the toxic effects of this regimen in these patients.

- Determine the disease-free and overall survival of patients treated with this regimen.

- Determine whether abnormal cytogenetics at presentation correlate with poor response in
patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF)
subcutaneously (SC) beginning on day 5 and continuing until peripheral blood stem cell
(PBSC) collection is complete.

Approximately 2-4 weeks after PBSC collection, patients receive melphalan IV over 15-30
minutes on day -2. Patients then undergo autologous PBSC transplantation (PBSCT) on day 0.
Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

Approximately 2-4 months after autologous PBSCT, patients receive fludarabine IV over 30
minutes on days -7 to -3 and cyclophosphamide IV over 1 hour on days -4 to -3. Patients
undergo allogeneic PBSCT on day 0. Patients receive G-CSF SC beginning on day 7 and
continuing until blood counts recover.

Patients receive graft-vs-host disease (GVHD) prophylaxis comprising oral tacrolimus twice
daily on days -1 to 90 followed by a taper on days 91-150 and methotrexate IV on days 1, 3,
and 6.

After day 120, patients with stable or progressive disease and no evidence of active GVHD
may receive donor lymphocyte infusion (DLI) over 2 hours. Patients may receive up to 3 DLIs
every 8 weeks.

Patients are followed every 3 months for 3 years, every 6 months for 5 years, and then
annually for 15 years.

PROJECTED ACCRUAL: A maximum of 63 patients will be accrued for this study.