Clofarabine, Idarubicin, Cytarabine, Vincristine Sulfate, and Dexamethasone in Treating Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia

PRIMARY OBJECTIVES:

I. To evaluate the response rate of the chemotherapy regimen in patients with mixed phenotype
acute leukemia.

SECONDARY OBJECTIVES:

I. To evaluate the durability of response, the overall and event-free survival rates, and the
safety profile of the regimen.

OUTLINE:

INDUCTION THERAPY: Patients receive clofarabine intravenously (IV) over 60 minutes on days
1-4 or 1-3; idarubicin IV over 30-60 minutes on days 1-3 or 1-2; cytarabine IV over 2 hours
on days 1-4; vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and
dexamethasone IV over 10-30 minutes on days 1-4 and 15-18. Patients with a certain type of
leukemia may receive rituximab IV over 4-6 hours on days 1 and 8 or sorafenib tosylate orally
(PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for up to 2 courses.

CONSOLIDATION THERAPY: Patients receive clofarabine IV over 60 minutes on days 1-3 or 1-2;
idarubicin IV over 30-60 minutes on days 1-2; cytarabine IV over 2 hours on days 1-3 or 1-2;
vincristine sulfate IV over 15-30 minutes on days 1, 8, and 15; and dexamethasone IV over
10-30 minutes on days 1-4 and 15-18. Patients with a certain type of leukemia may receive
rituximab IV over 4-6 hours on days 1 and 8 of courses 1-3 or sorafenib tosylate PO BID on
days 1-28 of course 1-6 and beyond. Treatment repeats every 28 days for up to 6 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Inclusion Criteria:

- Sign an informed consent document

- Newly diagnosed or relapsed mixed phenotype acute leukemia (MPAL), which for this
protocol, will be defined as follows: bone marrow result interpreted by the reading
pathologist (or tissue biopsy for cases of extramedullary disease) as: biphenotypic
leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia,
leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other
diagnosis indicating the presence of multiple lineages within the cell population

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 at study entry

- Adequate organ function as outlined below (unless due to leukemia)

- Serum creatinine =< 3 mg/dL

- Total bilirubin =< 2.5 mg/dL

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and/or
aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3
x upper limit of normal (ULN) or =< 5 x ULN if related to disease

- Women of childbearing potential must have a negative serum or urine pregnancy test
within 7 days; women of childbearing potential and men must agree to use contraception
at study entry and for the duration of active study treatment

- Cardiac ejection fraction >= 40% (by either cardiac echocardiogram [echo] or multi
gated acquisition [MUGA] scan); documentation of recent (=< 6 months from screening)
outside reports is acceptable

- If newly diagnosed, prior therapy with hydrea and/or steroid and the use of a single
or a two day dose of cytarabine (up to 3 g/m^2), for emergency use up to 24 hours
prior to start of study therapy is allowed

Exclusion Criteria:

- Breast feeding females

- Patients with active, uncontrolled infections

- Patients with active secondary malignancy will not be eligible unless approved by the
principal investigator