Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I

Treatment will consist of 4 main phases: Remission Induction, Consolidation, Reinduction, and
Maintenance. High risk patients will receive a reintensification phase prior to transplant in
first remission.

REMISSION INDUCTION: Chemotherapy will be given in an attempt to induce the participant's
leukemia into remission. Drugs given are intrathecal triple drug treatment with methotrexate,
hydrocortisone and Ara-C (ITMHA); dexamethasone; vorinostat; bortezomib; PEG-asparaginase;
mitoxantrone; cyclophosphamide; cytarabine; and 6-mercaptopurine.

CONSOLIDATION PHASE: After the participant's blood counts have recovered from Remission
Induction, he/she will move to the consolidation phase. This therapy is given to kill any
remaining leukemia cells. Drugs given are ITMHA, high-dose methotrexate, and
6-mercaptopurine.

RE-INDUCTION: This phase aims to improve the participant's overall response to therapy by
again seeking to bring his/her leukemia into remission. Drugs given are ITMHA, mitoxantrone,
peg-asparaginase, dexamethasone, bortezomib, and vorinostat.

RE-INTENSIFICATION: If the participant's maximum residual disease (MRD) is not negative after
consolidation, he/she will receive intensification therapy, then go on to stem cell
transplant (SCT) (SCT not part of this study).

MAINTENANCE PHASE: Participants with negative MRD after consolidation will skip the
re-intensification phase and proceed to receive maintenance therapy to keep the leukemia from
returning. Drugs given are ITMHA, dexamethasone, vincristine, 6-mercaptopurine and
methotrexate. Each cycle of these drugs lasts 28 days and will be repeated up to 20 times as
long as there are no serious side effects.

Inclusion Criteria:

- Patient is ≤ 365 days of age at the time of diagnosis.

- Patient has newly diagnosed acute lymphoblastic leukemia (ALL) or acute
undifferentiated leukemia with ≥25% blasts in the bone marrow (M3), with or without
extramedullary disease. Patients with T-cell ALL are eligible. Patients with bilineage
or biphenotypic acute leukemia are eligible, provided the morphology and
immunophenotype are predominantly lymphoid.

- Limited prior therapy, including systemic glucocorticoids for one week or less, one
dose of vincristine, and one dose of intrathecal chemotherapy.

- Written informed consent following Institutional Review Board, NCI, FDA, and Office
for Human Research Protections (OHRP) Guidelines.

Exclusion Criteria:

- Patients with prior therapy, other than therapy specified in the Inclusion Criteria.

- Patients with mature B-cell ALL or acute myelogenous (AML).

- Patients with Down syndrome.

- Inability or unwillingness of legal guardian/representative to give written informed
consent.