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

INCLUSION CRITERIA

   - Voluntary written informed consent

   - Female subjects who:

      - Are postmenopausal for at least 1 year before the screening visit, OR

      - Are surgically sterile, OR

      - If they are of childbearing potential, agree to practice 2 effective methods of
      contraception, at the same time, from the time of signing the informed consent
      form through 30 days after the last dose of bortezomib, or agree to completely
      abstain from heterosexual intercourse

   - Male subjects, even if surgically sterilized (ie, status post vasectomy) who:

      - Agree to practice effective barrier contraception during the entire study
      treatment period and through a minimum of 30 days after the last dose of study
      drug, OR

      - Agree to completely abstain from heterosexual intercourse

   - • Relapsed or refractory B or T cell acute lymphoblastic leukemia that has progressed
   following at least one prior therapy. Ph+ patients are eligible. Relapsed ALL is
   defined in patients as the reappearance of leukemia cells in the peripheral blood or
   bone marrow or appearance of extramedullary disease after a complete remission.
   Refractory ALL is defined in patients as failure to achieve a complete remission after
   induction therapy. Complete remission is defined by <5% leukemia cells in the bone
   marrow with recovery of peripheral blood counts. Relapsed disease can be documented by
   bone marrow biopsy (>5% cells in the bone marrow) or by flow cytometry in the
   peripheral blood or biopsy of extramedullary disease.

   - Has received at least 1 line of prior systemic therapy that may NOT have included
   bortezomib (Velcade); patients who have undergone autologous/allogeneic stem cell
   transplantation are eligible

   - Transplant-eligible patients are eligible

   - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

   - No poorly-controlled intercurrent illness including, but not limited to, ongoing or
   active infection, poorly controlled diabetes, symptomatic congestive heart failure, or
   psychiatric illness that in the opinion of the investigator would limit compliance
   with study requirements

   - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper
   limit of normal (ULN)

   - Total bilirubin ≤ 1.5 x (ULN unless elevation is deemed due to leukemia infiltration)

   - Adequate renal function defined as creatinine clearance of ≥ 30 mL/minute by the
   Cockcroft-Gault method

EXCLUSION CRITERIA

   - > 1.5 x ULN total bilirubin

   - ≥ Grade 2 peripheral neuropathy

   - 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; prior to study entry, any
   electrocardiogram (ECG) abnormality at screening must be documented by the
   investigator as not medically relevant

   - Hypersensitivity to bortezomib, boron, or mannitol

   - Pregnant or lactating

   - Serious medical or psychiatric illness likely to interfere with participation in this
   clinical study

   - Diagnosed or treated for another malignancy within 2 years of enrollment, with the
   exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
   the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

   - Participation in clinical trials with other investigational agents not included in
   this trial throughout the duration of this trial

   - Radiation therapy within 3 weeks before randomization; enrollment of subjects who
   require concurrent radiotherapy (which must be localized in its field size) should be
   deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
   date of therapy

   - Prior exposure ≥ 350 mg/m² of anthracycline (doxorubicin equivalent)

   - Left ventricular ejection fraction < 40%