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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00103285




Registration number
NCT00103285
Ethics application status
Date submitted
7/02/2005
Date registered
8/02/2005
Date last updated
14/06/2021

Titles & IDs
Public title
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Scientific title
Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)
Secondary ID [1] 0 0
NCI-2009-00302
Secondary ID [2] 0 0
AALL0331
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: Group 0 Induction Therapy - All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) \< 0.1% OR MRD \>= 0.1% and \< 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD \>= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study.

Active comparator: Group 1-SR-low ALL, Arm I (combination chemotherapy) - Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years

Experimental: Group 1-SR-low ALL, arm II (combination chemotherapy) - Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.

Active comparator: Group 2-SR-avg ALL, arm I (combination chemotherapy) - Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.

Experimental: Group 2-SR-avg ALL, arm II (combination chemotherapy) - Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.

Active comparator: Group 2-SR-avg ALL, arm III (combination chemotherapy) - Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.

Active comparator: Group 2-SR-avg ALL, arm IV (combination chemotherapy) - Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.

Experimental: Group 3-SR-high ALL, combination chemotherapy - Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.


Treatment: Other: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IV or SC

Treatment: Drugs: Dexamethasone
Given IV or PO

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV or IT

Treatment: Drugs: Leucovorin Calcium
Given PO

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IM or IT

Treatment: Drugs: Pegaspargase
Given IM

Treatment: Drugs: Thioguanine
Given PO

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

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS) for SR-Average ALL Patients
Timepoint [1] 0 0
6 years
Primary outcome [2] 0 0
Event-free Survival (EFS) for SR-Low Patients
Timepoint [2] 0 0
6 years
Secondary outcome [1] 0 0
Health-related Quality of Life Relative to Physical, Social and Emotional Impairment
Timepoint [1] 0 0
At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
Secondary outcome [2] 0 0
Event-Free Survival Probability According to MRD Status End Induction (Day 29)
Timepoint [2] 0 0
MRD at Day 29 of therapy
Secondary outcome [3] 0 0
Overall Survival Probability (OS) According to Induction Day 29 MRD Status
Timepoint [3] 0 0
Overall Survival Probability of 6 years
Secondary outcome [4] 0 0
Early Marrow Status (EMS) by MRD Status End Induction (Day 29)
Timepoint [4] 0 0
Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
Secondary outcome [5] 0 0
Optimal Time Point for Advance Health Related Quality of Life Intervention
Timepoint [5] 0 0
At 1 month after diagnosis and 3 months post-therapy.
Secondary outcome [6] 0 0
Event-free Survival (EFS) for SR-High Patients.
Timepoint [6] 0 0
6 years
Secondary outcome [7] 0 0
Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)
Timepoint [7] 0 0
6 years

Eligibility
Key inclusion criteria
* Patients must be enrolled on AALL03B1 prior to enrollment on AALL0331
* Initial white blood cells (WBC) < 50,000/ul
* Newly diagnosed B-precursor acute lymphoblastic leukemia

* Standard-risk (SR) disease meeting 1 of the following criteria:
* SR-average by age and WBC
* No unfavorable features
* Rapid early responder (RER) by day 15
* CNS 1 or 2
* Minimal residual disease (MRD) negative on day 29
* Trisomies of 4, 10, and 17 or TEL-AML1 translocation and RER and CNS2 allowed
* SR-low by age and WBC
* No unfavorable features
* RER by day 15
* MRD negative on day 29
* CNS1
* Favorable cytogenetics-trisomies of 4, 10, and 17 or TEL-AML translocation
* SR-high
* Unfavorable features meeting = 1 of the following criteria:

* MLL rearrangements and RER
* Steroid pretreatment
* CNS3
* Slow early responder by morphology or MRD
* Patients with Down syndrome are allowed
* Patients with overt testicular disease are not eligible for this study, but may be eligible for AALL0232
* Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment
* Patients receiving prior steroid therapy may be eligible for AALL0331 study
* Patients with a contraindication to additional asparaginase therapy, following Induction, are not eligible for the Standard Risk-Low study, and should be removed from protocol therapy at the end of Induction
* Patients who are assigned to the standard risk-average group following Induction and who meet the HRQOL
* Age at diagnosis >= 2 years (note that this is a more restrictive age range than for the therapeutic component of the study)
* At least one parent with reading comprehension of English or Spanish languages for which validated surveys exist
* Diagnosis at one of the institutions participating in this limited institution correlative study
* A parent or legal guardian must sign a written informed consent/parental permission for all patients
* 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
9 Years
Sex
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
11/04/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/03/2021
Sample size
Target
Accrual to date
Final
5377
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
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
State/province [13] 0 0
Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kansas
Country [17] 0 0
United States of America
State/province [17] 0 0
Kentucky
Country [18] 0 0
United States of America
State/province [18] 0 0
Louisiana
Country [19] 0 0
United States of America
State/province [19] 0 0
Maine
Country [20] 0 0
United States of America
State/province [20] 0 0
Maryland
Country [21] 0 0
United States of America
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Massachusetts
Country [22] 0 0
United States of America
State/province [22] 0 0
Michigan
Country [23] 0 0
United States of America
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Minnesota
Country [24] 0 0
United States of America
State/province [24] 0 0
Mississippi
Country [25] 0 0
United States of America
State/province [25] 0 0
Missouri
Country [26] 0 0
United States of America
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Nebraska
Country [27] 0 0
United States of America
State/province [27] 0 0
Nevada
Country [28] 0 0
United States of America
State/province [28] 0 0
New Hampshire
Country [29] 0 0
United States of America
State/province [29] 0 0
New Jersey
Country [30] 0 0
United States of America
State/province [30] 0 0
New Mexico
Country [31] 0 0
United States of America
State/province [31] 0 0
New York
Country [32] 0 0
United States of America
State/province [32] 0 0
North Carolina
Country [33] 0 0
United States of America
State/province [33] 0 0
North Dakota
Country [34] 0 0
United States of America
State/province [34] 0 0
Ohio
Country [35] 0 0
United States of America
State/province [35] 0 0
Oklahoma
Country [36] 0 0
United States of America
State/province [36] 0 0
Oregon
Country [37] 0 0
United States of America
State/province [37] 0 0
Pennsylvania
Country [38] 0 0
United States of America
State/province [38] 0 0
Rhode Island
Country [39] 0 0
United States of America
State/province [39] 0 0
South Carolina
Country [40] 0 0
United States of America
State/province [40] 0 0
South Dakota
Country [41] 0 0
United States of America
State/province [41] 0 0
Tennessee
Country [42] 0 0
United States of America
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Texas
Country [43] 0 0
United States of America
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Utah
Country [44] 0 0
United States of America
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Vermont
Country [45] 0 0
United States of America
State/province [45] 0 0
Virginia
Country [46] 0 0
United States of America
State/province [46] 0 0
Washington
Country [47] 0 0
United States of America
State/province [47] 0 0
West Virginia
Country [48] 0 0
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
State/province [51] 0 0
Manitoba
Country [52] 0 0
Canada
State/province [52] 0 0
Newfoundland and Labrador
Country [53] 0 0
Canada
State/province [53] 0 0
Nova Scotia
Country [54] 0 0
Canada
State/province [54] 0 0
Ontario
Country [55] 0 0
Canada
State/province [55] 0 0
Quebec
Country [56] 0 0
Canada
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Saskatchewan
Country [57] 0 0
New Zealand
State/province [57] 0 0
Auckland
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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 different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. 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) may kill more cancer cells.
Trial website
https://clinicaltrials.gov/study/NCT00103285
Trial related presentations / publications
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.
Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013 Jun 27;121(26):5154-7. doi: 10.1182/blood-2013-02-485623. Epub 2013 May 15.
Public notes

Contacts
Principal investigator
Name 0 0
Kelly W Maloney
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/NCT00103285