Four Drug Reinduction With Bortezomib for Relapsed or Refractory ALL or LL in Children and Young Adults

Inclusion Eligibility Criteria

* Age: \> 1 and \< 40 years of age at the time of enrollment
* Diagnosis: Precursor B-cell ALL with bone marrow (BM) or combined BM/extramedullary relapse; T-cell ALL with relapsed disease; LL with relapsed disease, or ALL(T or pre-B) with primary refractory disease after at least two regimens
* Performance Score: 50% for patients
* Prior Therapy 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. In addition, the following requirements must be met:

Cytotoxic therapy: 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.

Biologic (anti-neoplastic) agent: At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI).

Stem cell transplant or rescue: No evidence of active graft-vs-host disease (GVHD) and ≥ 4 months must have elapsed from time of transplant. Must not be receiving GVHD prophylaxis.

* Adequate Organ Function Requirements
* Reproductive Function: Female patients of childbearing potential must have a negative pregnancy test confirmed within 2 weeks prior to enrollment, must agree not to breastfeed their infants while on this study.Male and female patients of child-bearing potential must agree to use 2 effective methods of contraception approved by the investigator, at the same time, from the time of signing the informed consent form and for a minimum of 6 months after study treatment, or agree to completely abstain from heterosexual intercourse.
* Signed written informed consent. Assent from children will be obtained per institutional guidance.

Exclusion Eligibility Criteria

* known allergy to any of the drugs on the study with the exception of PEG-asparaginase
* Isolated CNS or isolated testicular disease
* Systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
* Known optic nerve and/or retinal involvement
* Patients with concomitant genetic syndrome
* Cumulative prior anthracycline exposure must not exceed 400 mg/m2
* Patients who have previously received bortezomib or other proteasome inhibitors
* Patients taking anticonvulsants known to activate the cytochrome p450 system
* Patients who cannot receive any asparaginase products
* Patients who are pregnant or breast-feeding
* Patients with planned non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
* Patients with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
* Diagnosed or treated for another malignancy within 2 years of enrollment
* Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.Radiation therapy within 3 weeks before randomization.