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

Inclusion Criteria:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

• 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 (i.e., 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
• The patient has relapsed or refractory B or T cell acute lymphoblastic leukemia that has progressed following at least one prior therapy; Philadelphia chromosome-positive (Ph+) patients are eligible; relapsed ALL is defined in patients as the reappearance of leukemia cells in the peripheral blood or bone marrow 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
• Must have received at least one (1) line of prior systemic therapy that may NOT have included VELCADE (bortezomib); patients who have undergone autologous/allogeneic stem cell transplantation are eligible
• Transplant eligible patients are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• 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
• Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is due to leukemia infiltration as defined by characteristic radiographic appearance or liver biopsy
• Patients must have adequate renal function defined as creatinine clearance of 30 ml/minute (Cockcroft-Gault)

Exclusion Criteria:

• Patient has > 1.5 x ULN total bilirubin
• Patient has >= grade 2 peripheral neuropathy
• Patient had 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
• Patient has hypersensitivity to bortezomib, boron, or mannitol
• Female subject is 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
• The patient has been exposed to >= 350mg/m^2 of anthracycline (doxorubicin equivalent)
• The patient has a left ventricular ejection fraction of < 40%