Trial Information

Autologous Transplantation for Chronic Myelogenous Leukemia Using Retrovirally Marked Peripheral Blood Progenitor Cells Obtained After In Vivo Cyclophosphamide/G-CSF Priming

OBJECTIVES:

- Assess clinical outcomes, survival, and morbidity of transplantation therapy in
patients with chronic myelogenous leukemia when treated with high dose chemotherapy and
filgrastim (G-CSF) followed by autologous retrovirally transduced peripheral blood stem
cell (PBSC) transplantation.

- Determine whether this priming treatment can increase the fraction of benign
Philadelphia chromosome (Ph) negative hematopoietic progenitors in PBSC and reduce the
incidence of persistent or recurrent leukemia after autologous transplantation with
mobilized PBSC in these patients.

- Assess whether retroviral transduction of mobilized PBSC progenitors determines the
contribution of malignant Ph positive progenitors contaminating the graft to relapse
after transplantation in these patients.

- Determine whether this priming treatment can expand the benign progenitor population in
the PBSC collections from these patients.

OUTLINE: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day 1
and filgrastim (G-CSF) subcutaneously (SQ) daily beginning on day 4 and continuing until the
completion of leukapheresis. Peripheral blood stem cells (PBSC) are harvested 4-7 times
between days 10 and 21 beginning when blood counts recover (CD34+ cells are selected from 2
of these PBSC collections and transduced with the LN NEO virus prior to cryopreservation).

In the transplant phase, patients who have not received prior radiotherapy receive
cyclophosphamide IV over 2 hours daily on days -7 and -6 and total body irradiation on days
-4 through -1. Autologous PBSC and LN NEO transduced CD34+ cells are reinfused on day 0.
Patients also receive G-CSF IV daily beginning on day 0 and continuing until blood counts
recover.

Patients who have received prior radiotherapy receive oral busulfan every 6 hours on days
-10 through -7 and cyclophosphamide IV daily on days -6 through -3. Autologous PBSC and LN
NEO transduced CD34+ cells are reinfused on day 0. Patients also receive G-CSF IV daily
beginning on day 0 and continuing until blood counts recover.

All patients then receive interferon alfa SQ daily until disease progression or unacceptable
toxicity.

Patients are followed at 3 weeks; at 3, 6, 9, 12, 18, and 24 months; and then annually
thereafter.

PROJECTED ACCRUAL: A total of 4-26 patients will be accrued for this study.