Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

PRIMARY OBJECTIVES:

I. To determine the efficacy of dose-adjusted etoposide, prednisone, vincristine sulfate,
cyclophosphamide, and doxorubicin hydrochloride plus asparaginase (DA-EPOCH-A) in adults with
acute lymphoblastic leukemia/lymphoma (ALL).

SECONDARY OBJECTIVES:

I. To evaluate the safety and feasibility of this regimen.

OUTLINE:

Patients receive etoposide, doxorubicin hydrochloride, and vincristine sulfate intravenously
(IV) continuously over days 1-4, cyclophosphamide IV over 1 hour on day 5, and prednisone
orally (PO) twice daily (BID) on days 1-5. Patients also receive asparaginase intramuscularly
(IM) or IV over 1-2 hours every 2-3 days, beginning day 7 of each course. Patients who are
cluster of differentiation (CD)20 positive and Philadelphia chromosome negative also receive
rituximab IV on day 1 or 5. Patients who are Philadelphia chromosome positive also receive
imatinib mesylate PO on days 1-14. Treatment repeats every 21 days for up to 8 courses in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Patients must have a confirmed diagnosis of either B- or T-cell acute lymphoblastic
leukemia or lymphoblastic lymphoma that is either:

- Arm A: Initially diagnosed at age 40 or later, OR

- Arm B: Relapsed after or failed to respond to >= 1 previous chemotherapy regimen

- The regimen under study must constitute a reasonable therapeutic option

- Presence of >= 5% abnormal blasts in the bone marrow

- Patients with prior allogeneic hematopoietic cell transplantation (HCT) must be at
least 90 days post-HCT and must be on =< 20 mg of prednisone (or equivalent dose of an
alternative corticosteroid) for treatment/prevention of graft-vs-host disease

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN; unless attributable
to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at
which point total bilirubin must be =< 2.5 x ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3.0 x institutional ULN

- Note: Patients with liver test abnormalities attributable to hepatic involvement by
ALL will be permitted if the total bilirubin is =< 3.0 x ULN and ALT/AST are =< 5.0 x
ULN

- Creatinine =< 1.5 mg/dL; however, patients with a creatinine > 1.5 mg/dL but with a
calculated creatinine clearance of > 60 ml/min, as measured by the Modification of
Diet in Renal Disease (MDRD) equation, will be eligible

- Measurement of left ventricular ejection fraction (LVEF) should be performed in
patients with prior anthracycline exposure or known history of arrhythmia or
structural heart disease; in these cases, LVEF must be >= 40%

- As patients with ALL frequently have cytopenias, no hematologic parameters will be
required for enrollment or to receive the first cycle of treatment; however, adequate
recovery of blood counts will be required to receive subsequent cycles

- Per good clinical practice, any toxicity related to prior therapies that, in the
opinion of the investigator, would potentially be worsened with DA-EPOCH-A +/-
imatinib (imatinib mesylate) +/- rituximab, should be resolved to grade 1 or less

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Women of childbearing potential must have a negative pregnancy test and must agree to
the use of effective contraception while on treatment; men must also agree to the use
of effective contraception while on treatment

- Ability to give informed consent and comply with the protocol

- Anticipated survival of at least 3 months

Exclusion Criteria:

- Patients with Burkitt lymphoma/leukemia

- Patients must not have received chemotherapy within 14 days of enrollment, with the
two following exceptions:

- Routine systemic maintenance therapy (e.g., Abelson murine leukemia viral
oncogene homolog 1 [ABL] kinase inhibitor, methotrexate, 6-mercaptopurine,
vincristine, etc.) and intrathecal/intraventricular therapy

- Systemic therapy for the acute management of hyperleukocytosis or acute symptoms
(e.g., corticosteroids, cytarabine, etc.)

- May not have prior malignancies unless the expected survival is at least 2 years

- For patients with Philadelphia chromosome positive (Ph+) ALL, they must not have
progressed within 3 months of receiving imatinib or have a documented ABL kinase
mutation known to confer resistance to imatinib (e.g., T315I)

- Patients with persistent grade 2 or higher peripheral sensory or motor neuropathy of
any cause

- Patients with isolated extramedullary disease or with parenchymal central nervous
system (CNS) disease

- Known hypersensitivity or intolerance to any of the agents under investigation

- Human immunodeficiency virus (HIV) positive or evidence of infection with hepatitis B
or C virus, as defined by any of the following criteria (if patients have not
previously been tested for the following, these will be conducted during screening):

- HIV antibody positive

- Hepatitis B surface antigen or core antibody positive

- Hepatitis C antibody positive

- Other medical or psychiatric conditions that in the opinion of the investigator would
preclude safe participation in the protocol

- May not be pregnant or nursing