Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the efficacy and toxicities of flavopiridol (alvocidib) followed by ara-C
and mitoxantrone in adults with newly diagnosed acute myelogenous leukemia (AML) with
poor-risk features.

II. To determine the disease free and overall survival of patients exhibiting a response to
treatment with flavopiridol followed by ara-C and mitoxantrone.

OUTLINE:

Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72
hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Beginning
35-63 days after completion of course 1, patients achieving complete or partial remission
may receive a second course of treatment as above.

Patients age 50 and over with "core binding factor" acute myeloid leukemia (AML) (e.g.,
t[8;21], inv[16], or t[16;16]) achieving a complete remission after course 1 of treatment
may receive 3-4 courses of consolidation therapy comprising high-dose cytarabine at the
discretion of the investigator.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Adults with established, pathologically confirmed diagnoses of newly diagnosed,
poor-risk Acute Myeloid Leukemia(AML) including de novo and secondary Acute Myeloid
Leukemias but excluding newly diagnosed acute progranulocytic leukemia (APL, M3) will
be considered eligible for study

- ECOG performance status 0-2

- Patient must be able to give informed consent

- Serum creatinine =< 2.0

- ALT, AST =< 5 x upper limit of normal

- Bilirubin =< 2.0 mg/dl

- Left ventricular ejection fraction >= 45%

- Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL) with poor-risk
features, including:

- Age > 50 years, or age > 18 years with one or more of the following criteria:

- Antecedent hematologic disorder including myelodysplasia (MDS)-related AML
(MDS/AML) and prior myeloproliferative disorder (MPD)

- Treatment-related AML

- AML with trilineage dysplasia (AML-TLD)

- Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q,
21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13, complex karyotypes (>=
3 unrelated abnormalities)

Exclusion Criteria:

- Patients who have received hydroxyurea alone or have received non-cytotoxic therapies
previously for MDS or MPD (e.g., thalidomide or lenalidomide, interferon, cytokines,
low-dose 5-azacytidine, low-dose cytoxan) will be eligible for this trial

- Any previous treatment with flavopiridol

- Concomitant chemotherapy, radiation therapy, or immunotherapy

- Hyperleukocytosis with >= 50,000 blasts/uL; leukapheresis or hydroxyurea may be used
immediately prior to study drug administration for cytoreduction; must be stopped 24
hours before first dose of Flavopiridol

- Acute Progranulocytic Leukemia (APL, M3)

- Active CNS leukemia

- Active, uncontrolled infection; patients with infection under active treatment and
controlled with antibiotics are eligible

- Presence of other life-threatening illness

- Patients with mental deficits and/or psychiatric history that preclude them form
giving informed consent or from following protocol

- Pregnant and nursing patients are excluded