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

PRIMARY OBJECTIVES:

I. To examine the potential efficacy of DA-EPOCH as front-line therapy for adults with acute
lymphoblastic leukemia/lymphoma (ALL).

SECONDARY OBJECTIVES:

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

II. To evaluate the progression-free (PFS) and overall survival (OS) of patients after
receiving DA-EPOCH for newly-diagnosed ALL.

III. To explore for novel genetic/genomic biomarkers of prognosis and response to treatment
in adults with ALL.

IV. To compare outcomes predicted by the presence or absence of minimal residual disease
(MRD) as determined by either multiparameter flow cytometry (MFC) or high-throughput
sequencing (HTS).

OUTLINE:

Patients receive etoposide intravenously (IV) over 96 hours, doxorubicin IV over 96 hours,
and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide
IV over 1 hour on day 5 and prednisone orally (PO) twice a day (BID) on days 1-5. Patients
who are Philadelphia Chromosome positive (Ph+) also receive imatinib mesylate or dasatinib PO
once per day (QD) on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or
day 5. Courses repeat 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
every 6 months for 3 years.

Inclusion Criteria:

- Patients must have a confirmed diagnosis of either:

- Acute lymphoblastic leukemia

- Lymphoblastic lymphoma with detectable abnormal blasts in the bone marrow

- In the opinion of the treating investigator, patients must be an unsuitable candidate
for a pediatric-inspired regimen, reasons for which may include (but not be limited
to) older age (i.e., >= 40 years), practical/logistical barriers to or toxicity
concerns from administration of a pediatric-inspired regimen, or Ph+ disease

- Total bilirubin =< 2.0 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 =< 4.0 x ULN)

- Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 5.0 x institutional ULN; (Note: patients with liver test abnormalities attributable
to hepatic involvement by ALL will be permitted if the total bilirubin is =< 5.0 x ULN
and ALT/AST are =< 8.0 x ULN)

- Creatinine =< 2.0 mg/dL; however, patients with a creatinine > 2.0 mg/dL but with a
calculated creatinine clearance of > 30 ml/min, as measured by the Modification of
Diet in Renal Disease (MDRD) equation, will be eligible

- 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)

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2; (performance
status of 3 will be allowed if poor performance status is thought to be directly
secondary to ALL)

- Must agree to the use of effective contraception while on study treatment, unless they
are highly unlikely to conceive (defined as [1] surgically sterilized, or [2]
postmenopausal [i.e., a woman who is > 50 years old or who has not had menses for >= 1
year], or [3] not heterosexually active for the duration of the study)

- Ability to give informed consent and comply with the protocol

- Anticipated survival of at least 3 months, independent of ALL

Exclusion Criteria:

- Patients with Burkitt lymphoma/leukemia

- Patients must not have received any prior systemic therapy for ALL, except for the
acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids,
cytarabine, etc.)

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

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

- 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