RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
childhood acute lymphoblastic leukemia in remission B-cell childhood acute lymphoblastic leukemia	Drug: asparaginase  Drug: cyclophosphamide  Drug: cytarabine  Drug: daunorubicin  Drug: dexamethasone  Drug: doxorubicin  Drug: mercaptopurine  Drug: methotrexate  Drug: prednisone  Drug: thioguanine  Drug: vincristine  Procedure: chemotherapy	Phase III

Further Study Details: 

OBJECTIVES:

• Determine whether augmented BFM therapy is superior to ALinc 14/15 therapy in patients with newly diagnosed high-risk acute lymphoblastic leukemia.
• Determine whether minimal residual disease after induction therapy is predictive of an inferior prognosis in this patient population.
• Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

OUTLINE: This is a randomized study. Patients are stratified by CNS or testicular disease (yes vs no).

• Patients receive oral prednisone 3 times daily on days 1-29; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, 22; and asparaginase intramuscularly (IM) on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 or 3 disease also receive methotrexate IT on days 15 and 22. Patients with M1 bone marrow proceed to consolidation therapy. Patients achieving M2 bone marrow on day 29 receive oral prednisone 3 times daily on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 on day 43, then patient is off study.
• Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine subcutaneously (SQ) or IV on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine daily on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; asparaginase IM on days 15, 17, 19, 22, 24, 26, 43, 45, 47, 50, 52, and 54; and methotrexate IT on days 1, 15, 29, and 43. Patients then proceed to interim maintenance and delayed intensification on weeks 15-46. Courses repeat every 16 weeks.
• Maintenance I and II (weeks 15-22 and 31-38): Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; asparaginase IM on days 2, 12, 22, 32, and 42; and methotrexate IT on days 1 and 31.
• Delayed Intensification (weeks 23-36 and 39-42): Patients receive vincristine IV on days 57, 64, and 71; methotrexate IT on day 57; oral dexamethasone 2-3 times daily on days 57-63 and 71-77; doxorubicin IV over 15 minutes 3 times weekly on days 57, 64, and 71; and asparaginase IM on days 60, 62, 64, 67, 69, and 71.
• Delayed Intensification-Reconsolidation (weeks 27-30 and 43-46): Patients receive oral thioguanine on days 85-98; methotrexate IT on day 85; cyclophosphamide IV over 30 minutes on day 85; cytarabine IV or SQ on days 86-89 and 93-96; asparaginase IM on days 99, 101, 103, 106, 108, and 110; and vincristine IV on days 99 and 106.
• Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily for 5 consecutive days on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Patients with CNS 3 disease undergo whole brain radiotherapy (omit or discontinue mercaptopurine and IT methotrexate) on day 1. Testicular radiotherapy also begins on day 1.

Patients may receive oral methotrexate on day 1 of each course (if IT methotrexate is not administered).

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 3.1 years.

Ages Eligible for Study:  1 Year   -   21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell precursor acute lymphoblastic leukemia
• Registered on POG-9900 Classification Study
• Registered within 7 days of documenting complete response after induction on day 29 or, if 2 more weeks of induction are required, no later than day 49
• Classified as high risk:
• No simultaneous trisomy 4 and 10
• No TEL-AML1 gene
• Meets criteria for 1 of the following:
• Any age with WBC greater than 100,000/mm^3
• Age over 12 (boys) or 16 (girls)
• If younger, WBC must be 1 of the following:
• Greater than 80,000/mm^3 (for boys age 8 or girls age 12)
• Greater than 60,000/mm^3 (for boys age 9 or girls age 13)
• Greater than 40,000/mm^3 (for boys age 10 or girls age 14)
• Greater than 20,000/mm^3 (for boys age 11 or girls age 15)
• At least one of the following:
• CNS 3 disease (CSF WBC at least 5/microliter with blasts present)
• Testicular leukemia
• MLL gene rearrangements

PATIENT CHARACTERISTICS: Age:

• 1 to 21

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• See Disease Characteristics

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Lucile Packard Children's Hospital at Stanford, Palo Alto,  California,  94304,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143-0128,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Illinois
      Saint Jude Midwest Affiliate, Peoria,  Illinois,  61637,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
Oregon
      Doernbecher Children's Hospital, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0361,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

William Paul Bowman, MD,  Study Chair,  Cook Children's Medical Center - Fort Worth   

Study ID Numbers:  CDR0000067722; COG-P9906; POG-9906
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005603
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08