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

Fecha de inicio: 1 de enero de 2004

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