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NCT00103285 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2021-06-14

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Event-free Survival (EFS) for SR-Average ALL Patients

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outcome · POSTED

Event-free Survival (EFS) for SR-Low Patients

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outcome · POSTED

Health-related Quality of Life Relative to Physical, Social and Emotional Impairment

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outcome · POSTED

Event-Free Survival Probability According to MRD Status End Induction (Day 29)

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outcome · POSTED

Overall Survival Probability (OS) According to Induction Day 29 MRD Status

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outcome · POSTED

Early Marrow Status (EMS) by MRD Status End Induction (Day 29)

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outcome · POSTED

Optimal Time Point for Advance Health Related Quality of Life Intervention

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outcome · POSTED

Event-free Survival (EFS) for SR-High Patients.

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outcome · POSTED

Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
maximum Age
9 Years
minimum Age
1 Year
sex
ALL
std Ages
  1. CHILD
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: Cytarabine
    2. Drug: Dexamethasone
    3. Drug: Leucovorin Calcium
    4. Drug: Methotrexate
    5. Drug: Pegaspargase
    6. Drug: Vincristine Sulfate
    label
    Group 0 Induction Therapy
    type
    EXPERIMENTAL
  2. description
    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
    intervention Names
    1. Drug: Cyclophosphamide
    2. Drug: Cytarabine
    3. Drug: Dexamethasone
    4. Drug: Doxorubicin Hydrochloride
    5. Drug: Leucovorin Calcium
    6. Drug: Mercaptopurine
    7. Drug: Methotrexate
    8. Drug: Pegaspargase
    9. Drug: Thioguanine
    10. Drug: Vincristine Sulfate
    label
    Group 1-SR-low ALL, Arm I (combination chemotherapy)
    type
    ACTIVE_COMPARATOR
  3. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Dexamethasone
    3. Drug: Leucovorin Calcium
    4. Drug: Mercaptopurine
    5. Drug: Methotrexate
    6. Drug: Pegaspargase
    7. Drug: Vincristine Sulfate
    label
    Group 1-SR-low ALL, arm II (combination chemotherapy)
    type
    EXPERIMENTAL
  4. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Cytarabine
    4. Drug: Dexamethasone
    5. Drug: Doxorubicin Hydrochloride
    6. Drug: Leucovorin Calcium
    7. Drug: Mercaptopurine
    8. Drug: Methotrexate
    9. Drug: Pegaspargase
    10. Drug: Thioguanine
    label
    Group 2-SR-avg ALL, arm I (combination chemotherapy)
    type
    ACTIVE_COMPARATOR
  5. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Cytarabine
    4. Drug: Dexamethasone
    5. Drug: Doxorubicin Hydrochloride
    6. Drug: Leucovorin Calcium
    7. Drug: Methotrexate
    8. Drug: Pegaspargase
    9. Drug: Thioguanine
    10. Drug: Vincristine Sulfate
    label
    Group 2-SR-avg ALL, arm II (combination chemotherapy)
    type
    EXPERIMENTAL
  6. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Cytarabine
    4. Drug: Dexamethasone
    5. Drug: Doxorubicin Hydrochloride
    6. Drug: Leucovorin Calcium
    7. Drug: Mercaptopurine
    8. Drug: Methotrexate
    9. Drug: Pegaspargase
    10. Drug: Thioguanine
    11. Drug: Vincristine Sulfate
    label
    Group 2-SR-avg ALL, arm III (combination chemotherapy)
    type
    ACTIVE_COMPARATOR
  7. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Cytarabine
    4. Drug: Dexamethasone
    5. Drug: Doxorubicin Hydrochloride
    6. Drug: Leucovorin Calcium
    7. Drug: Mercaptopurine
    8. Drug: Methotrexate
    9. Drug: Pegaspargase
    10. Drug: Thioguanine
    11. Drug: Vincristine Sulfate
    label
    Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    type
    ACTIVE_COMPARATOR
  8. description
    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.
    intervention Names
    1. Radiation: 3-Dimensional Conformal Radiation Therapy
    2. Drug: Cyclophosphamide
    3. Drug: Cytarabine
    4. Drug: Dexamethasone
    5. Drug: Doxorubicin Hydrochloride
    6. Drug: Leucovorin Calcium
    7. Drug: Mercaptopurine
    8. Drug: Methotrexate
    9. Drug: Pegaspargase
    10. Drug: Thioguanine
    11. Drug: Vincristine Sulfate
    label
    Group 3-SR-high ALL, combination chemotherapy
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Group 1-SR-low ALL, arm II (combination chemotherapy)
    2. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    6. Group 3-SR-high ALL, combination chemotherapy
    description
    Some patients undergo cranial radiotherapy
    name
    3-Dimensional Conformal Radiation Therapy
    other Names
    1. 3-dimensional radiation therapy
    2. 3D Conformal
    3. 3D CONFORMAL RADIATION THERAPY
    4. 3D CRT
    5. 3D-CRT
    6. Conformal Therapy
    7. Radiation Conformal Therapy
    8. Radiation, 3D Conformal
    type
    RADIATION
  2. arm Group Labels
    1. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    2. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    6. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Carloxan
    4. Ciclofosfamida
    5. Ciclofosfamide
    6. Cicloxal
    7. Clafen
    8. Claphene
    9. CP monohydrate
    10. CTX
    11. CYCLO-cell
    12. Cycloblastin
    type
    DRUG
  3. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    7. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IV or SC
    name
    Cytarabine
    other Names
    1. .beta.-Cytosine arabinoside
    2. 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    3. 1-.beta.-D-Arabinofuranosylcytosine
    4. 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    5. 1-Beta-D-arabinofuranosylcytosine
    6. 1.beta.-D-Arabinofuranosylcytosine
    7. 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    8. 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    9. Alexan
    10. Ara-C
    11. ARA-cell
    12. Arabine
    type
    DRUG
  4. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 1-SR-low ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    7. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    8. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IV or PO
    name
    Dexamethasone
    other Names
    1. Aacidexam
    2. Adexone
    3. Aknichthol Dexa
    4. Alba-Dex
    5. Alin
    6. Alin Depot
    7. Alin Oftalmico
    8. Amplidermis
    9. Anemul mono
    10. Auricularum
    11. Auxiloson
    12. Baycadron
    type
    DRUG
  5. arm Group Labels
    1. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    2. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    6. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IV or IT
    name
    Doxorubicin Hydrochloride
    other Names
    1. 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  6. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 1-SR-low ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    7. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    8. Group 3-SR-high ALL, combination chemotherapy
    description
    Given PO
    name
    Leucovorin Calcium
    other Names
    1. Adinepar
    2. Calcifolin
    3. Calcium (6S)-Folinate
    4. Calcium Folinate
    5. Calcium Leucovorin
    6. Calfolex
    7. Calinat
    8. Cehafolin
    9. Citofolin
    10. Citrec
    11. Citrovorum Factor
    12. Cromatonbic Folinico
    type
    DRUG
  7. arm Group Labels
    1. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    2. Group 1-SR-low ALL, arm II (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    6. Group 3-SR-high ALL, combination chemotherapy
    description
    Given PO
    name
    Mercaptopurine
    other Names
    1. 3H-Purine-6-thiol
    2. 6 MP
    3. 6 Thiohypoxanthine
    4. 6 Thiopurine
    5. 6-Mercaptopurine
    6. 6-Mercaptopurine Monohydrate
    7. 6-MP
    8. 6-Purinethiol
    9. 6-Thiopurine
    10. 6-Thioxopurine
    11. 6H-Purine-6-thione, 1,7-dihydro- (9CI)
    12. 7-Mercapto-1,3,4,6-tetrazaindene
    type
    DRUG
  8. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 1-SR-low ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    7. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    8. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IM or IT
    name
    Methotrexate
    other Names
    1. Abitrexate
    2. Alpha-Methopterin
    3. Amethopterin
    4. Brimexate
    5. CL 14377
    6. CL-14377
    7. Emtexate
    8. Emthexat
    9. Emthexate
    10. Farmitrexat
    11. Fauldexato
    12. Folex
    type
    DRUG
  9. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 1-SR-low ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    7. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    8. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IM
    name
    Pegaspargase
    other Names
    1. L-Asparaginase with Polyethylene Glycol
    2. Oncaspar
    3. Oncaspar-IV
    4. PEG-Asparaginase
    5. PEG-L-Asparaginase
    6. PEG-L-Asparaginase (Enzon - Kyowa Hakko)
    7. PEGLA
    8. Polyethylene Glycol L-Asparaginase
    9. Polyethylene Glycol-L-Asparaginase
    type
    DRUG
  10. arm Group Labels
    1. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    2. Group 2-SR-avg ALL, arm I (combination chemotherapy)
    3. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    6. Group 3-SR-high ALL, combination chemotherapy
    description
    Given PO
    name
    Thioguanine
    other Names
    1. 2-Amino 6MP
    2. 2-Amino-1,7-dihydro-6H-purine-6-thione
    3. 2-Amino-6-mercaptopurine
    4. 2-Amino-6-purinethiol
    5. 2-Aminopurin-6-thiol
    6. 2-Aminopurine-6(1H)-thione
    7. 2-Aminopurine-6-thiol
    8. 2-Aminopurine-6-thiol Hemihydrate
    9. 2-Mercapto-6-aminopurine
    10. 6-Amino-2-mercaptopurine
    11. 6-Mercapto-2-aminopurine
    12. 6-Mercaptoguanine
    type
    DRUG
  11. arm Group Labels
    1. Group 0 Induction Therapy
    2. Group 1-SR-low ALL, Arm I (combination chemotherapy)
    3. Group 1-SR-low ALL, arm II (combination chemotherapy)
    4. Group 2-SR-avg ALL, arm II (combination chemotherapy)
    5. Group 2-SR-avg ALL, arm III (combination chemotherapy)
    6. Group 2-SR-avg ALL, arm IV (combination chemotherapy)
    7. Group 3-SR-high ALL, combination chemotherapy
    description
    Given IV
    name
    Vincristine Sulfate
    other Names
    1. Kyocristine
    2. Leurocristine Sulfate
    3. Leurocristine, sulfate
    4. Oncovin
    5. Vincasar
    6. Vincosid
    7. Vincrex
    8. Vincristine, sulfate
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
5377
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Event-free Survival (EFS) for SR-Average ALL Patients
    time Frame
    6 years
  2. description
    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.
    measure
    Event-free Survival (EFS) for SR-Low Patients
    time Frame
    6 years
secondary Outcomes
  1. description
    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.
    measure
    Health-related Quality of Life Relative to Physical, Social and Emotional Impairment
    time Frame
    At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
  2. description
    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.
    measure
    Event-Free Survival Probability According to MRD Status End Induction (Day 29)
    time Frame
    MRD at Day 29 of therapy
  3. description
    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.
    measure
    Overall Survival Probability (OS) According to Induction Day 29 MRD Status
    time Frame
    Overall Survival Probability of 6 years
  4. description
    Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative)
    measure
    Early Marrow Status (EMS) by MRD Status End Induction (Day 29)
    time Frame
    Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
  5. description
    Percentage of patients with elevated Anxiety.
    measure
    Optimal Time Point for Advance Health Related Quality of Life Intervention
    time Frame
    At 1 month after diagnosis and 3 months post-therapy.
  6. description
    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.
    measure
    Event-free Survival (EFS) for SR-High Patients.
    time Frame
    6 years
  7. description
    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.
    measure
    Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)
    time Frame
    6 years
Full study description
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.
detailed Description
PRIMARY OBJECTIVES: I. To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival (EFS) of children with SR-average acute lymphoblastic leukemia (ALL). II. Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL. III. To determine whether the addition of four doses of percutaneous endoscopic gastrostomy (PEG) asparaginase, given once every three weeks during Consolidation and Interim Maintenance phases, will improve the EFS for children with SR-low ALL. SECONDARY OBJECTIVES: I. 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. II. Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur. III. Correlate day 29 minimal residual disease (MRD) with EFS and overall survival (OS) of patients treated with these regimens. IV. Correlate early marrow response with day 29 MRD status. V. To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM). VI. To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials. OUTLINE: This is a 2-part, partially randomized, multicenter study. Patients are stratified according to early response to study induction therapy (rapid early response \[standard risk (SR)-low or SR-average acute lymphoblastic leukemia (ALL)\] vs slow early response \[SR-high ALL\]). After completion of induction therapy but before proceeding to part II therapy, patients are assigned to 1 of 3 groups based on stratification. PART I: 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. EXTENDED INDUCTION THERAPY: Patients receive dexamethasone IV or PO BID on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM on day 4, 5, or 6; and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1. Patients with M1 bone marrow and MRD \< 1% after extended induction therapy proceed to therapy in part II. Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study. PART II: GROUP 1 (SR-low ALL): Patients are randomized to 1 of 2 treatment arms. ARM I: STANDARD CONSOLIDATION THERAPY: Patients receive vincristine IV on day 1; mercaptopurine PO on days 1-28; and methotrexate IT on days 1, 8, and 15. Patients with Down syndrome (DS) receive leucovorin calcium (PO) at 48 and 60 hours after each dose of methotrexate IT. STANDARD INTERIM MAINTENANCE THERAPY: Patients receive vincristine IV on days 1 and 29; dexamethasone IV or PO BID on days 1-5 and 29-33; mercaptopurine PO on days 1-50; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, and 50; and methotrexate IT on day 29. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. STANDARD DELAYED INTENSIFICATION (DI) THERAPY: Patients receive vincristine IV on days 1, 8, and 15; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1 and 29. Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. ARM II: EXPERIMENTAL CONSOLIDATION THERAPY: Patients receive vincristine, mercaptopurine, methotrexate, and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22. EXPERIMENTAL INTERIM MAINTENANCE THERAPY: Patients receive vincristine, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36.Standard DI therapy: Patients receive standard DI therapy as in arm I. GROUP 2 (SR-average ALL): Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I. ARM II: STANDARD CONSOLIDATION THERAPY: Patients receive standard consolidation therapy as in group 1, arm I. Augmented interim maintenance therapy: Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Augmented DI therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6 AND day 43; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1, 29, and 36. Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. ARM III: INTENSIFIED CONSOLIDATION THERAPY: Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, 15\*, and 22\*. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT\*. NOTE: \*Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium. STANDARD INTERIM MAINTENANCE THERAPY: Patients receive standard interim maintenance therapy as in group 1, arm I. STANDARD DI THERAPY: Patients receive standard DI therapy as in group 1, arm I. ARM IV: INTENSIFIED CONSOLIDATION THERAPY: Patients receive intensified consolidation therapy as in group 2, arm III. AUGMENTED INTERIM MAINTENANCE THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II. AUGMENTED DI THERAPY: Patients receive augmented DI therapy as in group 2, arm II. GROUP 3 (SR-high ALL): Patients receive the following therapy: Intensified consolidation therapy: Patients receive intensified consolidation therapy as in group 2, arm III. AUGMENTED INTERIM MAINTENANCE\* THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses. NOTE: \*As of Amendment #7, all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with high-dose methotrexate (IM HD) rather than Capizzi methotrexate. Patients should then proceed to ADI 2 and then Maintenance. AUGMENTED DI\* THERAPY: Patients receive augmented DI therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses\*\*. NOTE: \*As of Amendment #7, all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with IM HD. Patients should then proceed to ADI 2 and then Maintenance. NOTE: \*\*Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only; these patients do not receive methotrexate on day 36, thioguanine, or leucovorin calcium. MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and methotrexate IT\* on day 1. Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients. NOTE: \*SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males. After the completion of study treatment, patients are followed every 1-2 months for 2 years, every 3 months for 1 year, and then every 6-12 months for 2 years.
Source references
references
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see Also Links
  1. label
    Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
Source notices and limitations
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        Updated: April 21, 2025
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