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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00005596




Registration number
NCT00005596
Ethics application status
Date submitted
2/05/2000
Date registered
27/01/2003
Date last updated
13/05/2016

Titles & IDs
Public title
Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
Scientific title
ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study
Secondary ID [1] 0 0
COG-P9905
Secondary ID [2] 0 0
9905
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - cytarabine
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - dexamethasone
Treatment: Drugs - leucovorin calcium
Treatment: Drugs - mercaptopurine
Treatment: Drugs - methotrexate
Treatment: Drugs - pegaspargase
Treatment: Drugs - thioguanine
Treatment: Drugs - vincristine sulfate

Experimental: Arm I - Patients receive IT methotrexate on day 1 followed by methotrexate IV over 20 minutes followed by methotrexate continuously over 23.6 hrs on wks 7, 10, 13, 16,19, and 22. At 42 hrs after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium every 6 hrs for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on wk 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of wks 8 and 17; and vincristine sulfate IV on day 1 of wks 8, 9, 17, and 18.

Experimental: Arm II - Patients receive methotrexate IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine sulfate, and IT methotrexate as in arm I.

Experimental: Arm III - Patients receive methotrexate IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of wk 16; oral mercaptopurine daily on wks 5-13, and from wk 24 until the completion of consolidation therapy. Patients also receive IT methotrexate as in arm I on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone 2x daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine sulfate IV on day 1 of wks 8, 9, 16, 17, 18, 28, and 29; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of wks 20 and 21; and oral thioguanine daily on wks 20-21.

Experimental: Arm IV - Patients receive methotrexate IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT methotrexate, dexamethasone, vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, cytarabine, and thioguanine as in arm III.


Treatment: Drugs: cyclophosphamide


Treatment: Drugs: cytarabine


Treatment: Drugs: daunorubicin hydrochloride
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC = 500/µL and platelets = 75,000/µL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression

Treatment: Drugs: dexamethasone
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.

Treatment: Drugs: leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.

Treatment: Drugs: mercaptopurine
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/µL and platelets > 75,000/uL

Treatment: Drugs: methotrexate
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22.
IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.

Treatment: Drugs: pegaspargase
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX

Treatment: Drugs: thioguanine
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.

Treatment: Drugs: vincristine sulfate
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Improvement in outcome in children receiving multidrug delayed-intensification therapy - The overall plan is to accrue for 3.1 years or until all accrual goals have been met, whichever occurs first. Since power is determined by event-rates, lower or higher than expected event rates could lead to an amendment to alter the accrual goal. This consideration will be made independent of arm-specific outcome, in order to eliminate bias
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Event-free survival, minimal residual disease, and early response - The test statistic will compare Kaplan-Meier curves. Cox multiple regression will be utilized.
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Occurrence of anticipated failures - An O'Brien-Fleming analysis will be conducted.
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Total grade 3+ central nervous system (CNS) toxicity rates based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Timepoint [3] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Confirmed diagnosis of newly diagnosed B-precursor acute lymphocytic leukemia

- Standard risk (not low, high, or very high risk)

- Prior registration and treatment on POG 9900 Classification Study

PATIENT CHARACTERISTICS:

Age:

- 1 to 21 at diagnosis

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

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

- Not specified

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified
Minimum age
1 Year
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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Arizona
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Arkansas
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California
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Connecticut
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Florida
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Georgia
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Hawaii
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Illinois
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Kansas
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Mississippi
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Missouri
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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Texas
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Vermont
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [35] 0 0
Alberta
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Canada
State/province [36] 0 0
Ontario
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Canada
State/province [37] 0 0
Quebec
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Netherlands
State/province [38] 0 0
Groningen
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Puerto Rico
State/province [39] 0 0
Santurce
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Switzerland
State/province [40] 0 0
Bern
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Switzerland
State/province [41] 0 0
Geneva

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

PURPOSE: This randomized phase III trial is comparing four regimens of combination
chemotherapy to see how well they work in treating children with newly diagnosed acute
lymphoblastic leukemia.
Trial website
https://clinicaltrials.gov/show/NCT00005596
Trial related presentations / publications
Chen IM, Harvey RC, Mullighan CG, Gastier-Foster J, Wharton W, Kang H, Borowitz MJ, Camitta BM, Carroll AJ, Devidas M, Pullen DJ, Payne-Turner D, Tasian SK, Reshmi S, Cottrell CE, Reaman GH, Bowman WP, Carroll WL, Loh ML, Winick NJ, Hunger SP, Willman CL. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2012 Apr 12;119(15):3512-22. doi: 10.1182/blood-2011-11-394221. Epub 2012 Feb 24.
Rabin KR, Gramatges MM, Borowitz MJ, Palla SL, Shi X, Margolin JF, Zweidler-McKay PA. Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012 Sep;59(3):468-74. doi: 10.1002/pbc.23395. Epub 2011 Nov 18.
Xu H, Cheng C, Devidas M, Pei D, Fan Y, Yang W, Neale G, Scheet P, Burchard EG, Torgerson DG, Eng C, Dean M, Antillon F, Winick NJ, Martin PL, Willman CL, Camitta BM, Reaman GH, Carroll WL, Loh M, Evans WE, Pui CH, Hunger SP, Relling MV, Yang JJ. ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol. 2012 Mar 1;30(7):751-7. doi: 10.1200/JCO.2011.38.0345. Epub 2012 Jan 30.
Borowitz MJ, Devidas M, Hunger SP, et al.: Prognostic signficance of end consolidation minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 26 (Suppl 15): A-10000, 2008.
Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, Linda S, Martin PL, Pullen DJ, Viswanatha D, Willman CL, Winick N, Camitta BM; Children's Oncology Group. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008 Jun 15;111(12):5477-85. doi: 10.1182/blood-2008-01-132837. Epub 2008 Apr 3.
Davies SM, Borowitz MJ, Rosner GL, Ritz K, Devidas M, Winick N, Martin PL, Bowman P, Elliott J, Willman C, Das S, Cook EH, Relling MV. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 15;111(6):2984-90. doi: 10.1182/blood-2007-09-114082. Epub 2008 Jan 8.
Hinds PS, Hockenberry MJ, Gattuso JS, Srivastava DK, Tong X, Jones H, West N, McCarthy KS, Sadeh A, Ash M, Fernandez C, Pui CH. Dexamethasone alters sleep and fatigue in pediatric patients with acute lymphoblastic leukemia. Cancer. 2007 Nov 15;110(10):2321-30.
Winick N, Martin PL, Devidas M, et al.: Delayed intensification (DI) enhances event-free survival (EFS) of children with B-precursor acute lymphoblastic leukemia (ALL) who received intensification therapy with six courses of intravenous methotrexate (MTX): POG 9904/9905: a Children's Oncology Group study (COG). [Abstract] Blood 110 (11): A-583, 2007.
Public notes

Contacts
Principal investigator
Name 0 0
Naomi J. Winick, MD
Address 0 0
Simmons Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications