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

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Pre-B acute lymphoblastic leukemia (ALL) in first early (< 36 months from diagnosis) isolated bone marrow or combined bone marrow/extramedullary relapse as documented by histology and immunophenotyping
  • T-cell ALL in first isolated bone marrow or combined relapse as documented by histology and immunophenotyping

  • T-cell lymphoblastic lymphoma in first relapse as documented by histology

    • Measurable disease as documented by clinical, radiographic, or histologic criteria
• Relapsed or refractory to conventional therapy

• No Ph+ ALL unless refractory to ≥ 1 tyrosine kinase inhibitor therapy

  • Patients who are unable to tolerate tyrosine kinase inhibitor therapy due to toxicity are eligible
• No mature B-cell ALL (i.e., sIg positive and kappa or lambda restricted positivity) with FAB L3 morphology and/or myc translocation

• No known optic nerve and/or retinal involvement

  • Patients presenting with visual disturbances should have an ophthalmological exam and, if indicated, an MRI to determine optic nerve or retinal involvement
• No extramedullary disease (i.e., isolated CNS disease or isolated testicular disease)
• No concurrent genetic syndrome (e.g., Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome)

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

  • 0.4 mg/dL (for patients 1 to 5 months of age)
  • 0.5 mg/dL (for patients 6 to 11 months of age)
  • 0.6 mg/dL (for patients 1 year of age)
  • 0.8 mg/dL (for patients 2 to 5 years of age)
  • 1 mg/dL (for patients 6 to 9 years of age)
  • 1.2 mg/dL (for patients 10 to 12 years of age)
  • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
  • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
• ALT < 3 times ULN for age (unless elevation due to leukemia infiltration)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
• Pulse oximetry ≥ 94% at sea level (> 90% if at high altitude)
• No evidence of dyspnea at rest or exercise intolerance
• No evidence of acute pulmonary infiltrates on chest radiograph
• No known allergy to doxorubicin, cytarabine, etoposide, etoposide phosphate, boron, mannitol, or bortezomib
• No CNS toxicity > grade 2
• Seizure disorder allowed provided patient is on anticonvulsants (e.g., benzodiazepines or gabapentin) and it is well controlled

• Able to receive any asparaginase products (E. coli, PEG-asparaginase, or Erwinia asparaginase) on this study (i.e., no prior severe pancreatitis, stroke, or other toxicity)

  • Patients who initially receive asparaginase but discontinue drug due to toxicity are eligible
  • Patients with prior allergies to pegaspargase that are clinically significant are eligible provided Erwinia L-asparaginase can be substituted

PRIOR CONCURRENT THERAPY:

• Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy (for patients who relapse on therapy other than standard ALL maintenance therapy)*
• No prior cumulative anthracycline exposure > 400 mg/m²
• No prior bortezomib or other proteasome inhibitors

• No prior reinduction attempts or treatment for prior extramedullary relapse

  • Patients with primary induction failure are not eligible
• At least 14 days since prior cytotoxic therapy (24 hours for hydroxyurea)
• At least 7 days since prior anticancer biologic agents or donor lymphocyte infusions

• At least 4 months since prior stem cell transplant or rescue

  • No evidence of active graft-vs-host disease (GVHD)
• No concurrent GVHD prophylaxis

• No concurrent anticonvulsants known to activate the cytochrome p450 system (e.g., phenytoin, carbamazepine, and phenobarbital)

  • Concurrent benzodiazepines or gabapentin allowed
• No concurrent corticosteroids (including steroids as antiemetics) except as treatment or prophylaxis for anaphylactic reactions OR treatment for pulmonary toxicity
• No other concurrent anticancer chemotherapy or immunomodulating agents NOTE: *Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to undergo a waiting period prior to entry onto this study.