A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias

Inclusion Criteria:

- 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

- Performance status - Karnofsky 50-100% (for patients age 11 to 21)

- Performance status - Lansky 50-100% (for patients age 10 and under)

- 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)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT ≤ 5 times ULN

- Albumin ≥ 2 g/dL

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

- 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

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection

- 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

- Recovered from prior chemotherapy

- At least 24 hours since prior hydroxyurea for cytoreduction

- At least 6 weeks since prior nitrosoureas

- No concurrent chemotherapy

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

- 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

- 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