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This phase II trial studies how well etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride with asparaginase work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Asparaginase breaks down the amino acid asparagine and may block the growth of tumor cells that need asparagine to grow. Giving combination chemotherapy with asparaginase may work better 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