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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00075725




Registration number
NCT00075725
Ethics application status
Date submitted
9/01/2004
Date registered
13/01/2004
Date last updated
27/04/2021

Titles & IDs
Public title
Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
Scientific title
High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
Secondary ID [1] 0 0
NCI-2009-00301
Secondary ID [2] 0 0
AALL0232
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
Adult B Acute Lymphoblastic Leukemia 0 0
Childhood B Acute Lymphoblastic 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 - Doxorubicin Hydrochloride
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Active comparator: Arm I - Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.

Active comparator: Arm II - Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.

Experimental: Arm III - Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5.

Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks.

Experimental: Arm IV - Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5.

Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks.


Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IT, SC, or IV

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Leucovorin Calcium
Given IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IT or IV

Treatment: Drugs: Pegaspargase
Given IM

Treatment: Drugs: Prednisone
Given PO or IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)
Timepoint [1] 0 0
5 Years
Secondary outcome [2] 0 0
Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Correlation of Early Marrow Response Status With MRD Positive.
Timepoint [3] 0 0
Day 29
Secondary outcome [4] 0 0
Correlation of Early Marrow Response Status With MRD Negative.
Timepoint [4] 0 0
Day 29
Secondary outcome [5] 0 0
Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).
Timepoint [6] 0 0
5 years

Eligibility
Key inclusion criteria
* Must be eligible for and enrolled on classification study COG-AALL03B1
* Newly diagnosed B-precursor acute lymphoblastic leukemia

* WBC > 50,000/mm^3 for patients age 1 to 9
* Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
* Whit blood cell (WBC) criteria:

* Age 1 - 9 years: WBC >= 50,000/uL
* Age 10 - 30 years: any WBC
* Prior steroid therapy: any WBC
* Testicular disease: any WBC
* Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
* Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Minimum age
1 Year
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with Down syndrome are ineligible to enroll onto this study

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
Single group
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
29/12/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/03/2021
Sample size
Target
Accrual to date
Final
3154
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [3] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5006 - North Adelaide
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
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California
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Colorado
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Connecticut
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Delaware
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United States of America
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District of Columbia
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United States of America
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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United States of America
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Iowa
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United States of America
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Kansas
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United States of America
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Kentucky
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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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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
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United States of America
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Oklahoma
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Oregon
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Pennsylvania
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United States of America
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Rhode Island
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United States of America
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South Carolina
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United States of America
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South Dakota
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United States of America
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Tennessee
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Texas
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United States of America
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Utah
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United States of America
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Vermont
Country [45] 0 0
United States of America
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Virginia
Country [46] 0 0
United States of America
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Washington
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United States of America
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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 [49] 0 0
Alberta
Country [50] 0 0
Canada
State/province [50] 0 0
British Columbia
Country [51] 0 0
Canada
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Manitoba
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Canada
State/province [52] 0 0
Newfoundland and Labrador
Country [53] 0 0
Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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New Zealand
State/province [57] 0 0
Auckland
Country [58] 0 0
New Zealand
State/province [58] 0 0
Christchurch
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New Zealand
State/province [59] 0 0
Wellington
Country [60] 0 0
Switzerland
State/province [60] 0 0
Bern
Country [61] 0 0
Switzerland
State/province [61] 0 0
Geneva
Country [62] 0 0
Switzerland
State/province [62] 0 0
Lausanne

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
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
Trial website
https://clinicaltrials.gov/study/NCT00075725
Trial related presentations / publications
Advani AS, Larsen E, Laumann K, Luger SM, Liedtke M, Devidas M, Chen Z, Yin J, Foster MC, Claxton D, Coffan K, Tallman MS, Appelbaum FR, Erba H, Stone RM, Hunger SP, McNeer JL, Loh ML, Raetz E, Winick N, Carroll W, Larson RA, Stock W. Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia. Blood Adv. 2021 Jan 26;5(2):504-512. doi: 10.1182/bloodadvances.2020002439.
Wood B, Wu D, Crossley B, Dai Y, Williamson D, Gawad C, Borowitz MJ, Devidas M, Maloney KW, Larsen E, Winick N, Raetz E, Carroll WL, Hunger SP, Loh ML, Robins H, Kirsch I. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. Blood. 2018 Mar 22;131(12):1350-1359. doi: 10.1182/blood-2017-09-806521. Epub 2017 Dec 28.
Karol SE, Mattano LA Jr, Yang W, Maloney KW, Smith C, Liu C, Ramsey LB, Fernandez CA, Chang TY, Neale G, Cheng C, Mardis E, Fulton R, Scheet P, San Lucas FA, Larsen EC, Loh ML, Raetz EA, Hunger SP, Devidas M, Relling MV. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood. 2016 Feb 4;127(5):558-64. doi: 10.1182/blood-2015-10-673848. Epub 2015 Nov 20.
Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr, Relling MV. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood. 2015 Oct 8;126(15):1770-6. doi: 10.1182/blood-2015-05-643601. Epub 2015 Aug 11.
Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, Nachman JB, Carroll AJ, Heerema NA, Gastier-Foster JM, Willman CL, Dai Y, Winick NJ, Hunger SP, Carroll WL, Larsen E. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015 Aug 20;126(8):964-71. doi: 10.1182/blood-2015-03-633685. Epub 2015 Jun 29.
Fernandez CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.
Public notes

Contacts
Principal investigator
Name 0 0
Eric C Larsen
Address 0 0
Children's Oncology Group
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00075725