Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Hypereosinophilic Syndrome
Intervention: alvocidib; cytarabine; mitoxantrone hydrochloride
Intervention description: Given IV; Given IV; Given IV
Intervention MeSH terms: Cytarabine; Mitoxantrone; Alvocidib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and how well giving alvocidib together with
      cytarabine and mitoxantrone works in treating patients with newly diagnosed acute myeloid
      leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, work
      in different ways to stop the growth of cancer cells, either by killing the cells or by
      stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill
      more cancer cells.
    

Eligibility criteria:

        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