Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00005603

Collaborator

National Cancer Institute (NCI) (NIH)

276

Enrollment

Locations

13.8

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in 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: Phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate	Phase 3

Detailed Description

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: Patients are stratified by CNS or testicular disease (yes vs no).

Induction therapy (weeks 1-5): 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.

Consolidation therapy (weeks 6-14): Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine subcutaneously (SC) 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 SC 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.
Continuation therapy (weeks 47-130): 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 or who are within 24 months of diagnosis with an initial WBC ≥ 100,000/mm^3 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

276 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study

Study Start Date :

Mar 1, 2000

Actual Primary Completion Date :

Sep 1, 2005

Outcome Measures

Primary Outcome Measures

Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy []
To determine for patients at high risk for treatment failure if the augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy, on the basis of historical controls.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 > 100,000/mm^3
CNS and bone marrow evaluations required for those patients with WBC > 100,000/mm^3 who are within 24 months of initial diagnosis
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

Contacts and Locations

Locations

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