Trial Information

Pilot Study of Intensive Chemotherapy Followed by Peripheral Blood Stem Cell Harvesting for Autotransplantation of Adults With Chronic Myelogenous Leukemia and High Risk Acute Leukemia

OBJECTIVES: I. Determine safety and toxicity of induction and transplant regimens in
patients with chronic myelogenous leukemia or high-risk acute leukemia. II. Determine
efficacy of collecting peripheral blood stem cells (PBSC) during early hematopoietic
recovery from intensive chemotherapy as a means for in vivo enrichment for cytogenetically
normal progenitor cells in this patient population. III. Correlate cytogenetic and molecular
responses in the peripheral blood and bone marrow with clinical response, time to
progression, and survival in these patients at several timepoints before and after
myelosuppressive and myeloablative therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (chronic
myelogenous leukemia vs acute lymphoblastic leukemia vs acute myelogenous leukemia).
Patients receive cytarabine IV over 4 hours, etoposide IV over 1.5-2 hours, and idarubicin
IV over 5-10 minutes on days 1, 3, and 5. Filgrastim (G-CSF) is administered subcutaneously
(SC) daily beginning on day 2 and continuing until blood counts recover. Chronic myelogenous
leukemia: On day 14 following chemotherapy, if bone marrow biopsy shows less than 20%
cellularity and a peripheral blood sample contains greater than 50% cytogenetically normal
cells, patients receive a second induction course followed by apheresis. Patients with less
than 50% cytogenetically normal cells are also considered for a second induction course.
Patients with no response or progressive disease are removed from the study. Acute leukemia:
On day 14 following chemotherapy, if bone marrow biopsy shows less than 20% cellularity and
the peripheral blood sample shows 100% cytogenetically normal cells, patients receive a
second induction course followed by apheresis. Patients with high risk disease in first
remission at time of study entry undergo apheresis during recovery from first course of
induction therapy and second course may be omitted. Patients receive second induction course
followed by G-CSF as after first induction course. Once blood counts recover, patients
undergo harvest of peripheral blood stem cells (PBSC). Patients also undergo bone marrow
stem cell collection in case of failure of PBSC transplantation (PBSCT). Patients receive
the following conditioning regimen: total body irradiation twice a day on days -8 to -5;
etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 2 hours on day -2. PBSCT
is conducted on day 0. G-CSF SC is administered beginning on day 1 and continues until blood
counts recover. Patients receive maintenance therapy with interferon alfa SC 3 times a week
for 12 months. Patients are followed weekly for 3 months and then monthly until death.

PROJECTED ACCRUAL: Approximately 15 patients will be accrued for this study.