STI571 in Treating Patients With Recurrent Leukemia

RATIONALE: Imatinib mesylate may interfere with the growth of cancer cells and may be an effective treatment for leukemia.

PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent leukemia.

OBJECTIVES:

* Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with recurrent Philadelphia chromosome-positive leukemia.
* Characterize the pharmacokinetic behavior of this drug in this patient population.
* Determine preliminarily the antileukemic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral imatinib mesylate (STI571) once daily for 28 days. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of STI571 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 32 patients will be accrued for this study within 3.5 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Recurrent Philadelphia (Ph) chromosome-positive leukemia

  * Recurrent or refractory acute lymphoblastic or myeloblastic leukemia OR
  * Chronic myelogenous leukemia with resistance to interferon alfa with any of the following:

    * WBC at least 20,000/mm\^3 after at least 3 months of interferon therapy
    * At least 100% increase in WBC to at least 20,000/mm\^3 confirmed over 2 weeks while receiving interferon alfa
    * At least 66% Ph chromosome-positive cells after 1 year of interferon therapy
    * At least 30% increase in number of Ph chromosome-positive cells after an interferon-induced response while continuing interferon therapy

PATIENT CHARACTERISTICS:

Age:

* Under 22

Performance status:

* Karnofsky 50-100% if over 10 years of age OR
* Lansky 50-100% if 10 years of age and under

Life expectancy:

* At least 8 weeks

Hematopoietic:

* See Disease Characteristics

Hepatic:

* Bilirubin no greater than 1.5 times normal
* SGPT less than 3 times normal
* Albumin greater than 2 g/dL

Renal:

* Creatinine no greater than 1.5 times normal OR
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* If prior allogeneic stem cell transplantation, no uncontrolled graft-versus -host disease
* No seizure disorder if on anticonvulsants
* No uncontrolled infection
* No CNS toxicity greater than grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* See Disease Characteristics
* At least 1 week since prior biologic therapy and recovered
* At least 3 months since prior stem cell transplantation (SCT)
* At least 1 week since prior growth factors
* At least 1 week since prior interferon alfa

Chemotherapy:

* Recovered from prior chemotherapy
* At least 6 weeks since prior busulfan and nitrosoureas
* At least 2 weeks since prior homoharringtonine
* At least 1 week since low-dose cytarabine
* At least 2 weeks since prior moderate-dose cytarabine
* At least 4 weeks since prior high-dose cytarabine
* At least 3 weeks since all other prior cytotoxic chemotherapies
* No prior hydroxyurea

Endocrine therapy:

* Must be on a stable dose of steroids if received prior allogeneic SCT

Radiotherapy:

* Recovered from prior radiotherapy
* At least 2 weeks since prior local palliative radiotherapy (small port)
* At least 6 months since prior craniospinal radiotherapy
* At least 6 months since prior radiotherapy to 50% or more of the pelvis
* At least 6 weeks since other prior substantial bone marrow radiotherapy

Surgery:

* Not specified

Other:

* No other concurrent investigational agents
* No concurrent anticonvulsants