• Maximum tolerated dose and recommended phase II dose [ Designated as safety issue: Yes ]
• Toxicity as assessed by CTCAE 3.0 [ Designated as safety issue: Yes ]
• Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½) [ Designated as safety issue: No ]

• Maximum tolerated dose and recommended phase II dose
• Toxicity as assessed by CTCAE 3.0
• Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½)

• Antitumor activity [ Designated as safety issue: No ]
• Correlate apoptosis and NF-kB activation [ Designated as safety issue: No ]

• Antitumor activity
• Correlate apoptosis and NF-kB activation

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib in treating young patients with refractory or recurrent leukemia.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and recommended phase II dose of bortezomib in children with refractory or recurrent leukemia.
• Determine the toxic effects of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

Secondary

• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Determine, preliminarily, the biologic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, open-label, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 1.5-36 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed leukemia of 1 of the following types:

  • Acute lymphoblastic leukemia
  • Acute myeloid leukemia
  • Chronic myelogenous leukemia in blast crisis
• Relapsed or refractory disease
• Immunophenotypically confirmed disease, either at initial diagnosis or relapse
• More than 25% blasts in the bone marrow (M3 bone marrow)
• Active extramedullary disease (except leptomeningeal disease) allowed
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life available

PATIENT CHARACTERISTICS:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (for patients age 11 to 21) OR
• Lansky 50-100% (for patients age 10 and under)

Life expectancy

• Not specified

Hematopoietic

• Platelet count ≥ 20,000/mm^3*
• Hemoglobin ≥ 8.0 g/dL*
• WBC < 20,000/mm^3** (hydroxyurea for cytoreduction allowed)
• No hyperleukocytosis (i.e., WBC > 100,000/mm^3) NOTE: *Transfusion allowed

NOTE: **An exception may be made at the discretion of the investigator

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 5 times ULN
• Albumin ≥ 2 g/dL

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

• Creatinine based on age as follows:

  • ≤ 0.8 mg/dL for patients age 5 and under
  • ≤ 1.0 mg/dL for patients age 6 to 10
  • ≤ 1.2 mg/dL for patients age 11 to 15
  • ≤ 1.5 mg/dL for patients age 16 to 21

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy
• At least 7 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• At least 7 days since prior biologic agents
• At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-versus-host disease
• No concurrent prophylactic G-CSF during course 1 of study
• No concurrent immunotherapy
• No concurrent biologic therapy

Chemotherapy

• Recovered from prior chemotherapy
• At least 24 hours since prior hydroxyurea for cytoreduction
• At least 6 weeks since prior nitrosoureas
• No concurrent chemotherapy

Endocrine therapy

• At least 7 days since prior steroids (except as premedication prior to blood product transfusion)

Radiotherapy

• Recovered from prior radiotherapy
• At least 2 weeks since prior small port local palliative radiotherapy
• At least 3 months since prior total body irradiation, craniospinal irradiation, or irradiation to more than 50% of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 7 days since prior retinoids
• No other concurrent investigational agents
• No other concurrent anticancer agents

• No concurrent anticonvulsant medications known to activate the cytochrome p450 system (e.g., phenytoin, carbamazepine, or phenobarbital)

  • Concurrent benzodiazepines and gabapentin are allowed