Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

OBJECTIVES:

Primary

- Determine the complete response (CR) rate (CR and incomplete blood count recovery (CRi))
of patients with acute myeloid leukemia in first relapse treated with gemcitabine
hydrochloride and mitoxantrone hydrochloride.

Secondary

- Evaluate disease free and overall survival of patients with acute myeloid leukemia in
first relapse treated with this particular chemotherapy regimen.

- Assess hematologic and non-hematologic toxicity associated with this regimen.

- Assess laboratory correlates of drug resistance in patients with relapsed acute myeloid
leukemia.

- Assess the percentage of patients receiving subsequent bone marrow transplantation.

OUTLINE: This is an open-label, multicenter study.

Patients receive gemcitabine hydrochloride IV over 12 hours on day 1 and mitoxantrone
hydrochloride IV over 30-60 minutes on days 1, 2, and 3. After completion of a single course
of therapy, patients who achieve a complete response may receive 1 additional course of
therapy at the discretion of the treating physician.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Bone marrow examination or peripheral blood analysis confirming active acute myeloid
leukemia by WHO criteria

- No M3 acute myeloid leukemia

- Not a candidate for allogenic bone marrow transplantation

- Patient must be in first relapse after having received induction chemotherapy

- Received 1 or 2 courses with remission lasting at least 1 month

- Patients with chloromas or leukemia cutis are eligible

- No evidence of leptomeningeal involvement

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Liver enzymes (total bilirubin, aspartate aminotransferase (AST) and ALT) ≤ 2.5 times
the upper limits of normal

- Liver enzymes ≥ 2.5 are acceptable if physician documents that it is secondary to
the disease

- Serum creatinine ≤ 3 mg/dL

- No poorly controlled medical conditions that would seriously complicate compliance
with this study

- No other active primary malignancy other than carcinoma in situ of the cervix or basal
cell carcinoma of the skin

- No New York Heart Association grade III or IV cardiac problems, defined as congestive
heart failure or myocardial infarction within 6 months prior to start of study

- Pregnant or nursing women are ineligible

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- No documented history of human immunodeficiency virus (HIV) infection

- No history of chronic liver disease

- Ejection fraction ≥ 45%

- No significant history of non-compliance to medical regimens or inability to give
reliable informed consent

PRIOR CONCURRENT THERAPY:

- Previous treatment related toxicities should be resolved to grade 1 or better

- No other investigational agents within 14 days prior to the start of study

- No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to
start of study

- No major surgery within 2 weeks prior to start of study

- At least two weeks must have elapsed since the conclusion of radiation therapy and the
start of gemcitabine hydrochloride, provided the acute effects of radiation treatment
have been resolved