Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide in treating young patients with refractory or recurrent leukemia.

OBJECTIVES:

Primary

* Determine the maximum tolerated dose and recommended phase II dose of temozolomide in pediatric patients with refractory or recurrent leukemia.
* Determine the toxic effects of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.

Secondary

* Determine the antitumor activity of this drug in these patients.
* Determine the biologic activity and mechanism(s) of resistance to this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18-24 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed leukemia of any of the following types:

  * Acute lymphoblastic leukemia
  * Acute myeloid leukemia
  * Chronic myelogenous leukemia in blast crisis
* Refractory or recurrent disease
* Immunophenotypic confirmation of disease at initial diagnosis or recurrence
* More than 25% blasts in the bone marrow (M3)
* Active extramedullary disease allowed except for leptomeningeal disease
* No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* No active CNS disease

PATIENT CHARACTERISTICS:

Age

* 1 to 21

Performance status

* Karnofsky 50-100% (for patients \> 10 years of age)
* Lansky 50-100% (for patients ≤ 10 years of age)

Life expectancy

* Not specified

Hematopoietic

* WBC \< 30,000/mm\^3 (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator)
* Platelet count ≥ 20,000/mm\^3 (platelet transfusions allowed)
* Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)

Hepatic

* ALT ≤ 5 times upper limit of normal (ULN)
* Albumin ≥ 2 g/dL
* Bilirubin ≤ 1.5 times ULN

Renal

* Creatinine normal for age OR
* Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m\^2

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

* At least 7 days since prior biologic therapy, including immunotherapy
* At least 3 months since prior stem cell transplantation

  * No evidence of active graft-vs-host disease
* No concurrent biologic therapy
* No concurrent immunotherapy

Chemotherapy

* Recovered from prior chemotherapy
* At least 6 weeks since prior nitrosoureas
* Prior therapy with hydroxyurea allowed for up to 24 hours before initiation of study drug
* No other concurrent chemotherapy

Endocrine therapy

* Concurrent hydrocortisone or other corticosteroids allowed as premedications prior to blood product transfusions in patients with prior severe allergic reactions

Radiotherapy

* Recovered from prior radiotherapy
* No concurrent radiotherapy

Surgery

* Not specified

Other

* No other concurrent anticancer agents
* No other concurrent investigational drugs