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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00103285
Ethics application status
Date submitted
7/02/2005
Date registered
8/02/2005
Date last updated
11/07/2018

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:
B-cell Childhood Acute Lymphoblastic Leukemia 0 0
Untreated Childhood 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 - doxorubicin hydrochloride
Treatment: Other - 3-dimensional conformal radiation therapy
Treatment: Drugs - cytarabine
Treatment: Drugs - dexamethasone
Treatment: Drugs - pegaspargase
Treatment: Drugs - methotrexate
Treatment: Drugs - leucovorin calcium
Treatment: Drugs - mercaptopurine
Treatment: Drugs - cyclophosphamide
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 (vincristine sulfate, mercaptopurine and methotrexate. Patients with Down syndrome (DS) receive leucovorin calcium), standard interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine and methotrexate. Patients with DS receive leucovorin calcium), and standard delayed intensification (DI) therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine and methotrexate. Patients with DS receive dexamethasone, leucovorin calcium), 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 (vincristine sulfate, mercaptopurine, MTX, leucovorin calcium and pegaspargase), experimental interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine, MTX and pegaspargase), and standard DI therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine and MTX), 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 (vincristine sulfate, mercaptopurine and methotrexate. Patients with Down syndrome (DS) receive leucovorin calcium), standard interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine and methotrexate. Patients with DS receive leucovorin calcium), and standard delayed intensification (DI) therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine and methotrexate. Patients with DS receive dexamethasone, leucovorin calcium), 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 (vincristine sulfate, mercaptopurine and MTX. Patients with Down syndrome (DS) receive leucovorin calcium), augmented interim maintenance therapy (vincristine sulfate, MTX and pegaspargase. Patients with DS receive leucovorin calcium), augmented DI therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine, MTX. Patients with DS receive dexamethasone and leucovorin calcium), 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 (cyclophosphamide, cytarabine, mercaptopurine and vincristine sulfate, pegaspargase, MTX. Patients with DS receive oral leucovorin calcium), standard interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine and MTX. Patients with DS receive leucovorin calcium), and standard DI therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine and MTX. Patients with DS receive dexamethasone, leucovorin calcium), 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 IV-combination chemotherapy - Patients receive intensified consolidation therapy (cyclophosphamide, cytarabine, mercaptopurine and vincristine sulfate, pegaspargase, MTX. Patients with DS receive oral leucovorin calcium), augmented interim maintenance therapy (vincristine sulfate, MTX and pegaspargase. Patients with DS receive leucovorin calcium), and augmented DI therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine, MTX. Patients with DS receive dexamethasone and leucovorin calcium), 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 (cyclophosphamide, cytarabine, mercaptopurine and vincristine sulfate, pegaspargase, methotrexate. Patients with DS receive oral leucovorin calcium), augmented interim maintenance therapy (2 courses - vincristine sulfate, methotrexate and pegaspargase. Patients with DS receive leucovorin calcium), and augmented DI therapy (2 courses - vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine, methotrexate. Patients with DS receive dexamethasone and leucovorin calcium), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.


Treatment: Drugs: doxorubicin hydrochloride
Given IV or IT

Treatment: Other: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy

Treatment: Drugs: cytarabine
Given IV or SC

Treatment: Drugs: dexamethasone
Given IV or PO

Treatment: Drugs: pegaspargase
Given IM

Treatment: Drugs: methotrexate
Given IM or IT

Treatment: Drugs: leucovorin calcium
Given PO

Treatment: Drugs: mercaptopurine
Given PO

Treatment: Drugs: cyclophosphamide
Given IV

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
Event-free Survival (EFS) for SR-Average ALL Patients - EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Timepoint [1] 0 0
6 years
Primary outcome [2] 0 0
Event-free Survival (EFS) for SR-Low Patients - Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Timepoint [2] 0 0
6 years
Secondary outcome [1] 0 0
Health-related Quality of Life Relative to Physical, Social and Emotional Impairment - To identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.Standardized scores will be computed for child function using the gender and age-adjusted scores available from normative data from a healthy population of about 10,000 children. The various domains of family functioning will be assessed using well-validated instruments and analyzed as a dichotomous variable (impaired vs. non-impaired family functioning). Multiple regression analysis will be used to test the effect of family functioning (adjusted for therapy given, age at diagnosis, gender, socioeconomic status and other factors) on child function.
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) - Event-Free survival by Day 29 MRD status (negative vs positive), Event Free Probability (time from study entry to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
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 - Overall survival by Day 29 MRD status (negative vs positive), Overall survival defined as time from study entry to death or date of last contact for patients who are alive.
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) - Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative)
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 - Percentage of patients with elevated Anxiety.
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. - Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
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) - Event-free probability where EFS is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
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
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)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Childrens Hospital - 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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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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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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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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United States of America
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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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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
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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/show/NCT00103285
Trial related presentations / publications
Maloney KW, Larsen E, Mattano LA, et al.: Increased infection-related mortality for children with Down syndrome (DS) in contemporary Childrens Oncology Group (COG) acute lymphoblastic leukemia (ALL) clinical trials. [Abstract] Blood 108 (11): A-1865, 2006.
Public notes

Contacts
Principal investigator
Name 0 0
Kelly Maloney, MD
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
Other publications