Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed leukemia or lymphoma refractory to standard curative
treatment regimens

- Measurable or evaluable disease

- No meningeal leukemia or lymphoma

- No HIV-related lymphoma

- No lymphoproliferative diseases

PATIENT CHARACTERISTICS:

Age:

- 2 to 21

- Acute promyelocytic leukemia (APL) patients (stratum I) must be age 2 to 12

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin normal

- SGPT less than 2 times upper limit of normal

- No significant hepatic dysfunction that would preclude study therapy

Renal:

- Creatinine normal (age adjusted) OR

- Creatinine clearance at least 60 mL/min

- Potassium, magnesium, and calcium at least lower limit of normal (oral or IV
supplementation allowed)

- No significant renal dysfunction that would preclude study therapy

Cardiovascular:

- Rate corrected QTc interval no greater than 0.48 on EKG

- No significant cardiac dysfunction that would preclude study therapy

- No cardiac disease, including dysrhythmias

Pulmonary:

- No significant pulmonary dysfunction that would preclude study therapy

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No persistent grade 3 or greater sensory or motor neuropathy

- No prior grand mal seizures (grade 3 or greater) within the past 2 years other than
febrile seizures (except for patients with APL at discretion of investigator)

- No clinically significant unrelated systemic illness that would preclude study
therapy (e.g., serious infection)

- HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF],
sargramostim [GM-CSF], and epoetin alfa)

- No concurrent immunotherapy

Chemotherapy:

- No prior arsenic trioxide

- At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered

- No concurrent intrathecal chemotherapy except for acute promyelocytic leukemia (APL)
patients experiencing progressive meningeal leukemia and demonstrating benefit from
arsenic trioxide for systemic disease

- No other concurrent anticancer chemotherapy

Endocrine therapy:

- No concurrent steroids (except corticosteroids for retinoic acid syndrome)

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy

Surgery:

- Not specified

Other:

- At least 6 months since prior anticonvulsants

- At least 1 week since prior retinoid therapy

- No concurrent retinoids

- No other concurrent investigational agents