Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)

Inclusion Criteria The eligibility criteria listed below are interpreted literally and cannot be waived. 1. Age Patients must be \< 21 years of age when originally diagnosed with ALL. Patient must be \> 1 year of age at study entry. 2. Diagnosis Patients must have relapsed or refractory ALL with a M3 marrow (marrow blasts \>25%). Patients with CNS I, II or III or testicular disease are eligible. 3. Performance Level Karnofsky \> 50% for patients \> 10 years of age and Lansky \> 50% for patients \< 10 years of age. 4. Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. 1. Prior anthracycline exposure: Patients must have less than 400mg/m2 lifetime exposure of anthracycline chemotherapy. 2. Stem Cell Transplant (SCT): Patients are eligible after allogeneic stem cell transplant as long as patients are not actively being treated for graft-versus-host-disease (GvHD). 3. Patients should not have received previous therapy using bortezomib (Velcdade® or PS-341). 4. During the phase I portion of the trial, there is no limit on the number of prior treatment regimens. Patients with persistent disease after an induction attempt are eligible. 5. During the phase II portion of the trial, patients must have had two or more prior therapeutic attempts defined as: * Persistent initial disease after two induction attempts, or * Relapse after one-reinduction attempt (2nd relapse), or * Persistent disease after first relapse and initial re-induction attempt (Patients in first relapse are not eligible for the phase II portion of the study) 6. During the phase II portion of the trial, patients must have no more than 3 prior therapeutic attempts and it must be at least 3 months since the last treatment with a "VPLD" induction/re-induction regimen. 5. Reproductive Function 1. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. 2. Female patients with infants must agree not to breastfeed their infants while on this study. 3. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. Exclusion Criteria 1. Drug Allergies Patients will be excluded if they have allergies to the following: * Asparaginase products * Boron * Mannitol 2. Renal Function Patients will be excluded if their serum creatinine is \> 2 x the upper limit of normal for age at the institution's laboratory. 3. Liver/Pancreatic Function 1. Direct bilirubin \> 1.5x the institutional ULN for age. A total bilirubin result that is less than 1.5 times the institutional ULN for age may be used for eligibility if a direct bilirubin result is not available. 2. SGPT (ALT) \> 4 x institutional ULN 3. Grade 3 or greater pancreatitis as defined by the CTCAE v3.0 4. History of any L-asparaginase induced pancreatitis 5. Amylase or Lipase \> 2 x institutional ULN 4. Cardiac Function Patients will be excluded if their shortening fraction by echocardiogram is less than 30%. 5. Patients with Down Syndrome are excluded. 6. Infection * Patients will be excluded if they have an active uncontrolled infection. * Patients will be excluded if they have had a positive culture within 2 weeks of study entry. 7. Patients with grade 2 or greater motor or sensory neuropathy per CTC 3.0 criteria. 8. Patients planning on receiving other investigational agents while on this study. (An investigational agent is defined as any drug not currently approved for use in humans.) 9. Patients planning on receiving other anti-cancer therapies while on this study. Hydroxyurea for cyto-reduction is allowed prior to the start of therapy. 10. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. 11. Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.