• Complete remission (Phase II) [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the toxic effects of escalating doses of flavopiridol administered with cytarabine and mitoxantrone in patients with poor-risk acute leukemias.
• Determine whether this treatment induces clinical responses in these patients.
• Determine whether flavopiridol is directly cytotoxic to leukemic blasts in these patients.
• Determine whether flavopiridol can recruit and synchronize residual leukemic blasts to proliferate in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol. (Phase I closed to accrual effective10/24/2003).

Patients receive flavopiridol IV over 1 hour on days 1-3 and cytarabine IV continuously on days 6-9 followed by mitoxantrone IV over 30-150 minutes on day 9. Patients achieving a partial or complete response after the first course of therapy may receive an additional course of therapy beginning 35 ± 7 days after blood count recovery.

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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I closed to accrual effective 10/24/2003). Once the MTD is reached, additional patients are accrued to receive flavopiridol at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for phase I of the study (phase I closed to accrual effective 10/24/2003). A total of 53 patients will be accrued for phase II of the study.

DISEASE CHARACTERISTICS:

• One of the following histologically confirmed poor-risk acute leukemias:

  • Acute myelogenous leukemia (AML)

    • AML arising from myelodysplastic syndromes (MDS)
    • Secondary AML
    • Relapsed or refractory AML, including primary induction failure

  • Acute lymphoblastic leukemia (ALL)

    • Relapsed or refractory ALL, including primary induction failure
• No hyperleukocytosis with at least 50,000 leukemic blasts/mm^3
• Failure of primary induction therapy or relapse after achieving complete remission allowed if completed no more than 3 prior courses of induction/reinduction therapy
• No active CNS leukemia

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• No disseminated intravascular coagulation

Hepatic:

• AST and ALT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal
• Bilirubin no greater than 1.5 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No intrinsic impaired cardiac function including the following:

  • Myocardial infarction within the past 3 months
  • History of congestive heart disease or arrhythmia (regardless of time, severity, or resolution)
  • Cardiomyopathy
  • Class III or IV congestive heart failure
• LVEF at least 45% by MUGA or echocardiogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior autologous or allogeneic stem cell transplantation allowed provided at least 4 weeks since treatment and no presence of active graft-vs-host disease
• At least 4 days since prior hematopoietic growth factors (e.g., epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, or interleukin-11)
• Prior interferon allowed
• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior intensive chemotherapy except non-aplasia-producing agents (e.g., hydroxyurea or 6-methylpurine) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Prior thalidomide or imatinib mesylate allowed
• No other concurrent investigational or commercially-available antitumor therapy