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