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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
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United States of America
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Arizona
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Arkansas
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United States of America
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California
Country [5] 0 0
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Colorado
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
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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Iowa
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Kansas
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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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New York
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North Carolina
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North Dakota
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Ohio
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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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South Dakota
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Tennessee
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Texas
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Utah
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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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Wisconsin
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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New Zealand
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Auckland
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New Zealand
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Christchurch
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New Zealand
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Wellington
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Switzerland
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Bern
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Switzerland
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Geneva
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Switzerland
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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/ct2/show/NCT00103285
Trial related presentations / publications
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/ct2/show/NCT00103285