Trial Information

A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)

OBJECTIVES:

- Determine the effectiveness of induction with high-dose mitoxantrone and cytarabine in
patients with chronic myelogenous leukemia (CML) in blast crisis.

- Determine the toxicity and activity of consolidation with high-dose cyclophosphamide
and etoposide in these patients.

- Determine the toxicity and activity of maintenance with interferon alfa in these
patients.

- Determine the efficacy and tolerability of this regimen in these patients.

- Assess minimal residual disease by cytogenetics, DNA gene rearrangement (Southern
blotting), and polymerase chain reaction (PCR) in patients treated with this regimen,
and use semiquantitative PCR to evaluate the antileukemic activity of subsequent phases
of treatment in patients achieving complete remission.

OUTLINE: Patients are stratified by prior therapy for blast crisis (yes vs no).

- Induction: Patients receive high-dose cytarabine IV over 3 hours on days 1-5 and
mitoxantrone IV on day 3. Sargramostim (GM-CSF) is administered subcutaneously (SC) (or
IV over 4 hours) daily beginning on day 7 and continuing until blood counts recover.
After completion of induction, patients with a suitable HLA-identical bone marrow donor
undergo allogeneic bone marrow transplantation according to an appropriate IRB-approved
protocol. Patients without a donor proceed to consolidation approximately 4 weeks after
hospital discharge following induction.

- Consolidation: Patients receive high-dose cyclophosphamide IV on days 1-4 and etoposide
IV continuously on days 5-7. GM-CSF is administered SC (or IV over 4 hours) beginning
on day 8 and continuing until blood counts recover. Patients achieving a second chronic
phase or complete remission proceed to maintenance approximately 4 weeks after hospital
discharge following consolidation.

- Maintenance: Patients receive interferon alfa SC on day 1. Treatment with interferon
alfa continues daily in the absence of disease progression or unacceptable toxicity.

Patients with CNS involvement at entry or who develop CNS disease during the study receive
CNS therapy as outlined below.

- CNS therapy: Patients undergo whole brain irradiation as soon as possible but not
concurrently with mitoxantrone. Patients also receive methotrexate intrathecally 3
times a week until the CSF is clear, weekly for 4 weeks, and then monthly for 6 months.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 4 years.