Arsenic Trioxide for Induction Therapy of Adult Patients With Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have recurrent or refractory acute lymphoblastic leukemia or chronic myelogenous leukemia.

OBJECTIVES:

* Determine the rate of clinical and hematologic response in patients with Philadelphia chromosome-positive recurrent or refractory acute lymphoblastic leukemia or previously untreated or recurrent or refractory blastic phase chronic myelogenous leukemia when treated with arsenic trioxide.
* Determine the duration of hematologic response and overall survival of these patients when treated with this regimen.
* Determine the pattern of clinical adverse experience in these patients when treated with this regimen.
* Determine the pharmacokinetic profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive arsenic trioxide IV over 2-3 hours daily for 28 days. Patients who respond may receive a second course of therapy beginning 28 days from the last dose of the first course.

Patients are followed monthly for 3 months, every 2 months for 6 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 24-49 patients will be accrued for this study within 2.5 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of one of the following:

  * Acute lymphoblastic leukemia

    * Philadelphia chromosome (Bcr-abl) positive
    * Refractory to initial therapy OR recurrent following 1 induction therapy regimen with or without consolidation therapy and/or bone marrow transplantation
  * Blastic phase chronic myelogenous leukemia

    * Philadelphia chromosome (Bcr-abl) positive
    * Previously untreated OR recurrent or refractory following 1 induction therapy regimen with or without consolidation therapy including imatinib mesylate
* Must not be eligible for bone marrow transplant

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

* At least 8 weeks

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin no greater than 2.0 times upper limit of normal (ULN)
* AST/ALT no greater than 2 times ULN

Renal:

* Creatinine no greater than 2.0 times ULN
* Creatinine clearance greater than 70 mL/min

Cardiovascular:

* No uncontrolled angina
* No New York Heart Association class III or IV heart disease
* No second degree heart block without pacemaker

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after study
* HIV negative
* No uncontrolled infection or other serious concurrent illness
* No peripheral neuropathy
* No potassium less than 3.0 or greater than 5.5 mEq/L that can not be corrected OR
* No magnesium less than 1.2 or greater than 2.5 mEq/L that can not be corrected
* Electrolyte imbalances must be corrected prior to study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* See Disease Characteristics

Chemotherapy:

* See Disease Characteristics
* At least 28 days since prior chemotherapy
* At least 24 hours since prior hydroxyurea
* No prior arsenic trioxide
* No other concurrent cytotoxic chemotherapy except intrathecal chemotherapy for CNS leukemia

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 28 days since prior radiotherapy
* No concurrent radiotherapy including for palliation

Surgery:

* Not specified

Other:

* At least 14 days since prior imatinib mesylate
* No other concurrent investigational agents
* No concurrent amphotericin B