INCLUSION CRITERIA
Age: Patients with APL must be greater than or equal to 2 years and less than or equal to 12 (twelve) years of age. Patients with non-APL leukemia or lymphoma must be greater than or equal 2 years and less than or equal to 21 (twenty one) years of age.
Histological diagnosis: Patients must have a leukemia or lymphoma confirmed by morphologic analysis.
The leukemia/lymphoma must be refractory to standard curative treatment regimens.
Patients must have had their last dose of radiation therapy at least four weeks prior to study entry, their last dose of chemotherapy at least two weeks prior to study entry (four weeks for nitrosoureas), and their last dose of retinoids 7 days prior to study entry.
Patients must have recovered from the toxic effects of all prior therapy before entry onto this trial.
Patients should be off colony stimulating factors such as G-CSF, GM-CSF, and erythropoietin for at least one week prior to study entry.
Measurable/Evaluable disease: Patients must have measurable or evaluable disease.
Performance status: Patients should have an ECOG performance status of 0, 1, or 2.
Hepatic function: Patients must have adequate liver function, defined as bilirubin within normal limits, SGPT less than 2x the upper limit of normal.
Renal function: Patients must have an age-adjusted normal serum creatinine or a creatinine clearance greater than or equal to
60 mL/min/1.73 m(2).
Serum electrolytes: Potassium, magnesium and calcium must be equal to or greater than the lower limit of the normal range. Oral or intravenous supplementation may be used to normalize the serum electrolytes.
EKG: A rate corrected QT interval (QTc) less than or equal to 0.48.
Informed consent: All patients or their legal guardians (if the patient is less than 18) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility). When appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent.
EXCLUSION CRITERIA
Patients with meningeal leukemia/lymphomas (CSF WBC greater than 5/mm(3) and unequivocal confirmation of leukemic blasts in the CSF by morphologic demonstration on a CSF cytocentrifuge specimen). Patients with APL and meningeal disease may be entered following discussion with the PI or Protocol Chairman.
Patients with persistent grade greater than or equal to 3 sensory or motor neuropathy. Patients with APL and persistent grade 3 or 4 neuropathy may be entered following discussion with the PI or Protocol Chairman.
Patients with history of grand mal seizures (greater than or equal to grade 3) other than febrile seizures within the past 2 years. Patients must be off anticonvulsants for a minimum of 6 months. Patients with APL and history of seizures (greater than or equal to grade 3) may be entered following discussion with the PI or Protocol Chairman.
Clinically significant unrelated systemic illness (serious infections or significant cardiac (including dysrhythmias), pulmonary, hepatic, renal or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate arsenic trioxide or are likely to interfere with the study procedures or results.
Patients with cardiac disease including dysrhythmias. Patients with APL and history of cardiac disease may be entered following discussion with the PI or Protocol Chairman.
Patients with normal serum potassium, magnesium, and calcium levels and have a QTc greater than 0.48 after discontinuation of medications that may prolong the QTc interval.
Patients with known HIV infection or HIV related lymphoma or lymphoproliferative diseases are excluded from this trial due to unknown interaction of arsenic trioxide with antiretroviral medications and potential biological differences in lymphomas related to immune compromised states.
Pregnant or breast feeding females are not eligible because arsenic trioxide may be harmful to the developing fetus or nursing child.
Patients currently receiving other investigational agents.
Patients who previously received arsenic trioxide.
Warren Grant Magnuson Clinical Center (CC)