Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

PRIMARY OBJECTIVE:

I. Determine recommended phase II doses for the combination of flavopiridol and vorinostat in patients with acute leukemia, chronic myelogenous leukemia in blast crisis, or refractory anemia with excess blasts-2.

SECONDARY OBJECTIVES:

I. Determine the safety, toxicity, tolerability, and maximum tolerated dose of this drug regimen.

II. Determine the pharmacodynamic and clinical anti-leukemic effects of this drug regimen.

III. Correlate leukemia gene expression patterns with response in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour on days 1-5 and oral vorinostat three times daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Inclusion criteria

• Diagnosis of one of the following:

• Relapsed or refractory acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], or acute leukemia unclassifiable) following at least one prior systemic treatment
• Acute leukemia in a patient 60 years or older (no requirement for prior treatment)
• Acute leukemia that has evolved from a prior myelodysplastic syndrome
• Chronic myelogenous leukemia (CML) in blast crisis following prior imatinib mesylate therapy
• Refractory anemia with excess blasts-2 (RAEB-2)
• No known CNS leukemia
• ECOG performance status 0-2
• WBC < 50,000µL
• Hydroxyurea and/or leukaphereses may be used to lower WBC
• Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 50 mL/min
• Total bilirubin =< 2 times ULN
• AST/ALT =< 2.5 times ULN
• QTc interval =< 0.470 seconds
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No other condition that would preclude study participation
• At least 3 weeks since prior treatment (expect leukaphereses)
• No valproic acid therapy within the past 2 weeks
• No prior autologous or allogeneic bone marrow or stem cell transplantation
• No hydroxyurea use within the past 24 hours
• No concurrent treatment with other anti-cancer agents or investigational agents