RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy), and giving the drugs in different combinations may kill more cancer cells.

PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.

OBJECTIVES: Primary

• Determine the probability of 1-year continuous complete remission in patients with newly diagnosed acute lymphoblastic leukemia treated with first induction chemotherapy comprising daunorubicin, vincristine, prednisone, and pegaspargase; and second induction chemotherapy comprising high-dose cytarabine and mitoxantrone.

Secondary

• Determine the frequency and severity of toxic effects of these induction regimens followed by consolidation therapy comprising cyclophosphamide, cytarabine, mercaptopurine, and methotrexate and maintenance chemotherapy comprising mercaptopurine, methotrexate, vincristine, doxorubicin, dexamethasone, cyclophosphamide, thioguanine, and cytarabine in these patients.
• Determine, preliminarily, the significance of minimal residual disease as a prognostic factor for overall and relapse-free survival in patients treated with this regimen.
• Correlate, preliminarily, the pattern of gene expression with cytogenetic and fluorescent in situ hybridization risk classification and overall and relapse-free survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• : Patients receive daunorubicin IV on days 1-3; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally on days 1-28, followed by a taper to day 35; and pegaspargase IV or subcutaneously (SC) on day 15. Patients with CNS leukemia also receive methotrexate intrathecally (IT) or intraventricularly twice weekly and oral leucovorin calcium four times daily for 4 doses after each administration of methotrexate. When blasts are no longer present in the spinal fluid, patients receive methotrexate IT or intraventricularly once weekly for 4 weeks and then once monthly for 1 year. Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status or those with resistant disease proceed to second induction therapy.
• : Patients receive high-dose cytarabine IV on days 1-5; mitoxantrone IV on day 3; and filgrastim (G-CSF) SC or IV beginning on day 7 and continuing until blood counts recover. Patients with CNS leukemia also receive methotrexate and leucovorin calcium as in first induction chemotherapy. Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status with no extramedullary disease (other than CNS involvement) proceed to consolidation chemotherapy. Patients with resistant disease are removed from study. Patients with Philadelphia chromosome- or BCR/ABL-positive disease who achieve A1 bone marrow status and B1 peripheral blood status and who are eligible for and willing to participate in protocol are removed from this study.
• : Patients receive cyclophosphamide IV on days 1, 15, and 29; cytarabine IV on days 2-5 and 16-19; oral mercaptopurine on days 1-28; and methotrexate IT or intraventricularly on days 2, 9, 16, and 23. Patients with CNS leukemia also undergo cranial radiotherapy once daily, 5 days a week, for 2 weeks. Patients in complete remission proceed to maintenance chemotherapy.
• :
• Course 1: Patients receive oral mercaptopurine on days 1-63 and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients proceed to course 2 after blood counts recover.
• Course 2: Patients receive vincristine IV and doxorubicin IV on days 1, 8, 15, and 22 and oral dexamethasone on days 1-28. Patients proceed to course 3 after blood counts recover.
• Course 3: Patients receive cyclophosphamide IV on day 1; oral thioguanine on days 1-14; and cytarabine IV on days 3-6 and 10-13. Patients proceed to course 4 after blood counts recover.
• Course 4: Patients receive oral mercaptopurine once daily for 2 years and oral methotrexate once weekly for 2 years. Treatment continues in the absence of disease relapse or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study within 14 months.

Ages Eligible for Study:  18 Years   -   64 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Morphologically confirmed acute lymphoblastic leukemia (ALL), meeting any of the following criteria:
• FAB class L1 or L2 disease
• Mixed lineage ALL
• Newly diagnosed disease
• Patients with the following diagnoses are not eligible:
• FAB class L3 ALL
• Non-Hodgkin's lymphoma
• Chronic myelogenous leukemia in lymphoid blast crisis
• Mixed lineage acute myeloid leukemia
• Acute minimally differentiated myeloid leukemia (M0)
• Must be registered on protocols SWOG-9007 AND SWOG-S9910

PATIENT CHARACTERISTICS: Age

• 18 to 64

Performance status

• Zubrod 0-3

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No chronic liver disease
• Hepatitis panel, including hepatitis C, negative
• History of hepatitis A with positive antibody allowed

Renal

• Creatinine ≤ 2 times upper limit of normal OR
• Creatinine clearance > 40 mL/min

Cardiovascular

• Left ventricular function normal
• Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram
• No symptomatic congestive heart failure
• No coronary artery disease
• No cardiomyopathy
• No uncontrolled arrhythmia

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior remission induction chemotherapy for ALL
• Prior hydroxyurea to control WBC count allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other prior treatment for ALL