Arsenic Trioxide Therapy for Interferon Alpha Refractory or Intolerant Chronic Phase Chronic Myelogenous Leukemia

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of Philadelphia (Ph) chromosome positive (or breakpoint cluster region bcr
positive) chronic myelogenous leukemia in chronic phase

- Ineligible for or refused allogeneic bone marrow transplantation

- Interferon alfa refractory or intolerant as defined by the following:

- Refractory: Failure to achieve a complete hematologic response lasting for at least 1
month after prior therapy with interferon alfa based regimen for at least 3 months
65% or more Ph positive chromosomes in bone marrow after one year of interferon alfa
based therapy

- At least a 30% increase in Ph positive chromosomes in bone marrow in samples taken at
least one month apart OR

- An increase of at least 65% in Ph positive chromosomes in bone marrow

- Intolerant: Grade 3 or greater nonhematologic toxicity Autoimmune phenomenon at any
grade

- No accelerated phase or blastic phase disease as defined by the following:

- Greater than 15% blasts or basophils in the peripheral blood or bone marrow

- Greater than 30% blasts plus promyelocytes in the peripheral blood or bone marrow

- Documented extramedullary blastic disease outside liver or spleen

- Platelet count less than 100,000/mm3 unrelated to therapy

- Clonal evolution (additional chromosomal abnormalities other than Ph chromosome) as
solitary feature is not considered accelerated disease

- No known brain metastases or central nervous system (CNS) disease

PATIENT CHARACTERISTICS:

- Age: 12 and over

- Performance status: Zubrod 0-2

- Life expectancy: At least 2 years

- Hematopoietic: See Disease Characteristics

- Hepatic: Unless due to direct disease infiltration of the liver:

- ALT and AST no greater than 2.5 times upper limit of normal (ULN)

- Bilirubin no greater than 1.5 times ULN (unless due to Gilbert's disease)

- No hepatic disease that would preclude study

- Renal: Creatinine no greater than 1.5 times ULN Creatinine clearance at least 60
mL/min

- Cardiovascular: No history of New York Heart Association grade III or IV cardiac
disease

- No cardiovascular disease that would preclude study

- No unstable angina pectoris or cardiac arrhythmia that would shorten life expectancy

- Other: No history of grand mal seizures other than infantile febrile seizures

- No active secondary malignancy or other uncontrolled concurrent medical problem that
would shorten life expectancy

- No neurologic, endocrine, or other major systemic disease that would preclude study

- No active infection uncontrolled by oral or IV antibiotics

- No history of hypersensitivity to the study drug or drugs with similar chemical
structure

- No mental condition that would preclude study Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- Biologic therapy: See Disease Characteristics

- No concurrent bone marrow or peripheral blood stem cell transplantation

- Chemotherapy: At least 14 days since prior chemotherapy (48 hours for hydroxyurea and
6 weeks for busulfan) and recovered (unless evidence of rapidly progressive disease)

- No other concurrent cytotoxic chemotherapy

- No prior arsenic trioxide

- Endocrine therapy: No concurrent steroids for the treatment of neoplasms (except for
new adrenal failures)

- No concurrent hormones for the treatment of neoplasms (except for nondisease related
conditions)

- Radiotherapy: At least 14 days since prior radiotherapy

- No concurrent radiotherapy

- Surgery: Not specified

- Other: At least 14 days since other prior investigational agent

- No other concurrent investigational or antileukemic agents