Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Inclusion Criteria:

   - Diagnosis

      - Pre-B ALL in first early (< 36 months from diagnosis) isolated bone marrow (BM)
      or combined BM/extramedullary relapse; or

      - T-cell ALL in first isolated BM or combined relapse; or

      - T-LL in first relapse

   - Patients with leukemia must have had histologic verification of the malignancy at
   relapse, including immunophenotyping to confirm diagnosis

   - Patients with lymphoblastic lymphoma must have measurable disease documented by
   clinical, radiographic, or histologic criteria; patients must have relapsed or become
   refractory to conventional therapy

   - Patients must have a performance status corresponding to Eastern Cooperative Oncology
   Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and
   Lansky for patients =< 16 years of age

   - Patients who relapse while receiving standard ALL maintenance chemotherapy will not be
   required to have a waiting period before entry onto this study

   - Patients who relapse on therapy other than standard ALL maintenance therapy must have
   fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
   or radiotherapy prior to entering this study

   - At least 14 days since the completion of cytotoxic therapy with the exception of
   hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy

   - At least 7 days since the completion of therapy with a biologic agent or donor
   lymphocyte infusions (DLI); for agents that have known adverse events occurring beyond
   7 days after administration, this period must be extended beyond the time during which
   adverse events are known to occur

   - No evidence of active graft-vs-host disease (GVHD) and >= 4 months must have elapsed;
   must not be receiving GVHD prophylaxis

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
   mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

      - 1 month to < 6 months (0.4 male, 0.4 female)

      - 6 months to < 1 year (0.5 male, 0.5 female)

      - 1 to < 2 years (0.6 male, 0.6 female)

      - 2 to < 6 years (0.8 male, 0.8 female)

      - 6 to < 10 years (1 male, 1 female)

      - 10 to < 13 years (1.2 male, 1.2 female)

      - 13 to < 16 years (1.5 male, 1.4 female)

      - >= 16 years (1.7 male, 1.4 female)

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x
   ULN for age, unless elevation due to leukemia infiltration

   - Shortening fraction of >= 27% by echocardiogram, or

   - Ejection fraction of >= 50% by gated radionuclide study

   - No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >= 94%
   at sea level (> 90% if at high altitude)

   - No evidence of acute pulmonary infiltrates on chest radiograph

   - Patients with seizure disorder may be enrolled if on allowed anticonvulsants and well
   controlled; benzodiazepines and gabapentin are acceptable

   - Central nervous system (CNS) toxicity =< grade 2

   - Peripheral nervous system (PNS) toxicity < grade 3

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, FDA, and National Cancer Institute (NCI) requirements for human
   studies must be met

Exclusion Criteria:

   - Patients with Philadelphia chromosome positive ALL are not eligible unless refractory
   to at least one tyrosine kinase inhibitor (TKI) therapy; patients that are unable to
   tolerate TKI therapy due to toxicity are eligible

   - Patients with mature B-cell ALL, ie, leukemia with B-cell (soluble immunoglobulin
   [sIg] positive and kappa or lambda restricted positivity) ALL, with
   French-American-British (FAB) L3 morphology and/or a myc translocation, are not
   eligible

   - Extramedullary disease status: patients with isolated CNS disease or isolated
   testicular disease are not eligible

   - Patients with known optic nerve and/or retinal involvement are not eligible; patients
   presenting with visual disturbances should have an ophthalmological exam and, if
   indicated, an magnetic resonance imaging (MRI) to determine optic nerve or retinal
   involvement

   - Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi
   anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure
   syndrome are not eligible

   - Cumulative prior anthracycline exposure must not exceed 400 mg/m^2

   - Patients taking anticonvulsants known to activate the cytochrome p450 system, in
   particular anticonvulsants such as phenytoin, carbamazepine, and phenobarbital, are
   not eligible; benzodiazepines and gabapentin are acceptable

   - Patients who have previously received bortezomib or other proteasome inhibitors are
   not eligible

   - Patients who have a known allergy to doxorubicin, cytarabine, both etoposide and
   etopophos, boron, mannitol or bortezomib are not eligible

   - Patients who cannot receive any asparaginase products (E. Coli, PEG-asparaginase, or
   Erwinia asparaginase) on this study (eg, due to prior severe pancreatitis, stroke or
   other toxicity) are not eligible; patients who initially receive asparaginase, but
   must discontinue due to toxicity, remain eligible; patients with clinically
   significant prior allergies to pegaspargase are eligible if Erwinia L-asparaginase can
   be substituted

   - Patients who are pregnant or breast-feeding are not eligible for this study; negative
   pregnancy tests must be obtained in girls who are post-menarchal; males or females of
   reproductive potential may not participate unless they have agreed to use an effective
   birth control method

   - Patients must not have received any prior re-induction attempts and must not have
   received treatment for prior extramedullary relapse; patients with primary induction
   failure are not eligible