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NCT00005945 · CITED IN SOURCE DOCUMENTS

Comparison of Different Combination Chemotherapy Regimens in Treating Children With 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
2016-02-23

RATIONALE: Drugs used in chemotherapy use 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 childhood acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.

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.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Diagnosis of previously untreated B-cell precursor acute lymphoblastic leukemia * More than 25% L1 or L2 lymphoblasts * No more than 25% L3 lymphoblasts * WBC \< 50,000/mm\^3 * No T-cell precursor acute lymphoblastic leukemia by immunophenotyping * Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass allowed * CNS or testicular leukemia allowed * No patients found to have t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11-p12;q24) (characteristic of Burkitt's lymphoma) PATIENT CHARACTERISTICS: Age: * 1 to 9 Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Not specified Renal: * Not specified Other: * Not pregnant * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No more than 72 hours since prior intrathecal cytarabine Endocrine therapy: * At least 30 days since prior systemic corticosteroids given for more than 48 hours * Prior corticosteroids for mediastinal mass causing superior mediastinal syndrome allowed * Prior or concurrent inhaled corticosteroids allowed Radiotherapy: * Prior radiotherapy for mediastinal mass causing superior mediastinal syndrome allowed * No concurrent spinal radiotherapy Surgery: * Not specified
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
    Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: dexamethasone
    3. Drug: methotrexate
    4. Drug: pegaspargase
    5. Drug: vincristine sulfate
    label
    Induction Not Randomized
    type
    EXPERIMENTAL
  2. description
    Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: dexamethasone
    4. Drug: doxorubicin hydrochloride
    5. Drug: mercaptopurine
    6. Drug: methotrexate
    7. Drug: pegaspargase
    8. Drug: thioguanine
    9. Drug: vincristine sulfate
    10. Radiation: radiation therapy
    label
    Induction and Oral MTX, Double Delayed Intensification CNS
    type
    EXPERIMENTAL
  3. description
    Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses).
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: daunorubicin hydrochloride
    4. Drug: dexamethasone
    5. Drug: doxorubicin hydrochloride
    6. Drug: mercaptopurine
    7. Drug: methotrexate
    8. Drug: pegaspargase
    9. Drug: thioguanine
    10. Drug: vincristine sulfate
    11. Radiation: radiation therapy
    label
    Induction and Augmented regimen (IV MTX, Double DI)
    type
    EXPERIMENTAL
  4. description
    Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: dexamethasone
    4. Drug: doxorubicin hydrochloride
    5. Drug: mercaptopurine
    6. Drug: methotrexate
    7. Drug: pegaspargase
    8. Drug: thioguanine
    9. Drug: vincristine sulfate
    10. Radiation: radiation therapy
    label
    Induction and Oral MTX, Single Delayed Intensification
    type
    EXPERIMENTAL
  5. description
    Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: dexamethasone
    4. Drug: doxorubicin hydrochloride
    5. Drug: mercaptopurine
    6. Drug: methotrexate
    7. Drug: pegaspargase
    8. Drug: thioguanine
    9. Drug: vincristine sulfate
    10. Radiation: radiation therapy
    label
    Induction and Oral MTX, Double Delayed Intensification
    type
    EXPERIMENTAL
  6. description
    Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: dexamethasone
    4. Drug: doxorubicin hydrochloride
    5. Drug: mercaptopurine
    6. Drug: methotrexate
    7. Drug: pegaspargase
    8. Drug: thioguanine
    9. Drug: vincristine sulfate
    10. Radiation: radiation therapy
    label
    Induction and IV MTX, Single Delayed Intensification
    type
    EXPERIMENTAL
  7. description
    Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.
    intervention Names
    1. Drug: cyclophosphamide
    2. Drug: cytarabine
    3. Drug: dexamethasone
    4. Drug: doxorubicin hydrochloride
    5. Drug: mercaptopurine
    6. Drug: methotrexate
    7. Drug: pegaspargase
    8. Drug: thioguanine
    9. Drug: vincristine sulfate
    10. Radiation: radiation therapy
    label
    Induction and IV MTX, Double Delayed Intensification
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Induction Not Randomized
    2. Induction and Augmented regimen (IV MTX, Double DI)
    3. Induction and IV MTX, Double Delayed Intensification
    4. Induction and IV MTX, Single Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification
    6. Induction and Oral MTX, Double Delayed Intensification CNS
    7. Induction and Oral MTX, Single Delayed Intensification
    description
    Given IV
    name
    cyclophosphamide
    other Names
    1. Cytoxan
    2. NSC-26271
    type
    DRUG
  2. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    2. Induction and IV MTX, Double Delayed Intensification
    3. Induction and IV MTX, Single Delayed Intensification
    4. Induction and Oral MTX, Double Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification CNS
    6. Induction and Oral MTX, Single Delayed Intensification
    description
    Given IT
    name
    cytarabine
    other Names
    1. Cytosine Arabinoside
    2. Ara_C
    3. Cytosar-U
    4. NSC-63878
    type
    DRUG
  3. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    description
    Given IV
    name
    daunorubicin hydrochloride
    other Names
    1. Cerubidine
    2. NSC-82151
    type
    DRUG
  4. arm Group Labels
    1. Induction Not Randomized
    2. Induction and Augmented regimen (IV MTX, Double DI)
    3. Induction and IV MTX, Double Delayed Intensification
    4. Induction and IV MTX, Single Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification
    6. Induction and Oral MTX, Double Delayed Intensification CNS
    7. Induction and Oral MTX, Single Delayed Intensification
    description
    Given PO
    name
    dexamethasone
    other Names
    1. Decadron
    2. DM
    3. NSC-34521
    type
    DRUG
  5. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    2. Induction and IV MTX, Double Delayed Intensification
    3. Induction and IV MTX, Single Delayed Intensification
    4. Induction and Oral MTX, Double Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification CNS
    6. Induction and Oral MTX, Single Delayed Intensification
    description
    Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
    name
    doxorubicin hydrochloride
    other Names
    1. Adriamycin
    2. NSC-123127
    type
    DRUG
  6. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    2. Induction and IV MTX, Double Delayed Intensification
    3. Induction and IV MTX, Single Delayed Intensification
    4. Induction and Oral MTX, Double Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification CNS
    6. Induction and Oral MTX, Single Delayed Intensification
    description
    Given PO
    name
    mercaptopurine
    other Names
    1. 6-MP
    type
    DRUG
  7. arm Group Labels
    1. Induction Not Randomized
    2. Induction and Augmented regimen (IV MTX, Double DI)
    3. Induction and IV MTX, Double Delayed Intensification
    4. Induction and IV MTX, Single Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification
    6. Induction and Oral MTX, Double Delayed Intensification CNS
    7. Induction and Oral MTX, Single Delayed Intensification
    description
    Given PO and IT
    name
    methotrexate
    other Names
    1. MTX
    type
    DRUG
  8. arm Group Labels
    1. Induction Not Randomized
    2. Induction and Augmented regimen (IV MTX, Double DI)
    3. Induction and IV MTX, Double Delayed Intensification
    4. Induction and IV MTX, Single Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification
    6. Induction and Oral MTX, Double Delayed Intensification CNS
    7. Induction and Oral MTX, Single Delayed Intensification
    description
    Given IM
    name
    pegaspargase
    other Names
    1. PEG-asparaginase
    2. Oncaspar
    3. L-asparaginase with polyethylene glycol
    type
    DRUG
  9. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    2. Induction and IV MTX, Double Delayed Intensification
    3. Induction and IV MTX, Single Delayed Intensification
    4. Induction and Oral MTX, Double Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification CNS
    6. Induction and Oral MTX, Single Delayed Intensification
    description
    Given PO
    name
    thioguanine
    other Names
    1. 6 TG
    2. NSC-752
    type
    DRUG
  10. arm Group Labels
    1. Induction Not Randomized
    2. Induction and Augmented regimen (IV MTX, Double DI)
    3. Induction and IV MTX, Double Delayed Intensification
    4. Induction and IV MTX, Single Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification
    6. Induction and Oral MTX, Double Delayed Intensification CNS
    7. Induction and Oral MTX, Single Delayed Intensification
    description
    Given IV
    name
    vincristine sulfate
    other Names
    1. Oncovin
    2. NSC-67574
    3. VCR
    type
    DRUG
  11. arm Group Labels
    1. Induction and Augmented regimen (IV MTX, Double DI)
    2. Induction and IV MTX, Double Delayed Intensification
    3. Induction and IV MTX, Single Delayed Intensification
    4. Induction and Oral MTX, Double Delayed Intensification
    5. Induction and Oral MTX, Double Delayed Intensification CNS
    6. Induction and Oral MTX, Single Delayed Intensification
    description
    Undergo radiation therapy
    name
    radiation therapy
    other Names
    1. irradiation
    2. radiotherapy
    3. therapy
    4. radiation
    type
    RADIATION
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
3054
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The primary outcome index used in examining the randomized treatment groups will be event free survival (EFS) from the time of randomization (i.e., end of Consolidation), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.
    measure
    Event Free Survival
    time Frame
    Time of randomization
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy use 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 childhood acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.
detailed Description
OBJECTIVES: * Compare the event-free survival and overall survival of children with standard-risk acute lymphoblastic leukemia treated with escalating-dose IV methotrexate without leucovorin calcium versus oral methotrexate during the interim maintenance phase of therapy. * Compare the event-free survival and overall survival of these patients after receiving treatment in two delayed intensification phases versus one delayed intensification phase. * Compare the toxic effects of oral versus escalating-dose intravenous methotrexate in these patients. * Determine the prognostic significance of the rate of disappearance of peripheral lymphoblasts and lymphocytes during the first week of treatment in these patients. * Determine the prognostic significance of trisomies of chromosomes 4, 5, 10, and 17 and early treatment response in patients treated with these regimens. * Determine the prognostic significance of the TEL-AML1 fusion transcript and early treatment response in patients treated with these regimens. * Determine the minimal residual disease (MRD) by polymerase chain reaction in bone marrow and cerebrospinal fluid at various stages of therapy in these patients. * Determine the prognostic significance of MRD during various stages of therapy in these patients. * Determine whether a second delayed intensification therapy improves the prognosis of patients who have MRD at the end of induction therapy. OUTLINE: This is a randomized, multicenter study. Patients without CNS disease at diagnosis, achieving a specified early marrow response profile and M1 marrow status of less than 5% blasts in the bone marrow (regardless of the proportion of mature lymphocytes) by day 28 of induction therapy, and remaining event free with favorable bone marrow status and cytogenetics between day 21 and 28 of consolidation therapy are randomized to one of four treatment arms. Patients with CNS disease at diagnosis are assigned to treatment arm II and undergo cranial irradiation. Patients with any of the following unfavorable bone marrow features and/or unfavorable cytogenetic features are assigned to the augmented treatment regimen by day 21 of induction chemotherapy or at the beginning of consolidation chemotherapy: NOTE: All T-cell precursor patients that are not more than 4 months past completion of the delayed intensification phase of therapy should be switched to the augmented regimen as of 3/8/2004. These patients may be switched to the augmented regimen. The protocol gives specific instructions according to the phase of therapy the patients are actually in. * Unfavorable marrow status: * M2: 5-25% blasts in bone marrow at day 28 of induction chemotherapy (or at day 14 of induction chemotherapy if day 7 status is M3) OR * M3: More than 25% blast cell in bone marrow, regardless of the proportion of mature lymphocytes at day 14 of induction chemotherapy * Unfavorable cytogenetics: Must have 1 of the following: * t(9;22)(q34;q11) * t(4;11)(q21;q23) * Balanced t(1;19)(q23;p13) * Hypodiploidy with less than 45 chromosomes * Other 11q23 translocations involving MLL Patients receive standard induction chemotherapy comprising cytarabine (ARA-C) intrathecally (IT) on day 0 or up to 72 hours before day 0; oral dexamethasone (DM) twice daily on days 0-27; vincristine (VCR) IV on days 0, 7, 14, and 21; and pegaspargase (PEG-ASP) intramuscularly (IM) once between days 3-5. Patients without CNS disease at diagnosis receive methotrexate (MTX) IT on days 7 and 28. Patients with CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28. Patients who have achieved M1 marrow status by day 28 of induction therapy and have favorable early bone marrow response and cytogenetics proceed to standard consolidation therapy once blood counts have recovered. Patients with M3 bone marrow status at day 28 of induction therapy are taken off the protocol. All other patients are assigned to the augmented treatment regimen. Beginning on day 28 of induction chemotherapy, patients receive standard consolidation chemotherapy comprising VCR IV on day 0 and oral mercaptopurine (MP) on days 0-27. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation 5 days a week for 2 weeks. Patients with testicular disease receive bilateral testicular radiotherapy 5 days a week for 1 week and then for 3 consecutive days during the next week. NOTE: As of 3/8/2004, patients with T-cell disease who did not achieve M1 marrow status by day 14 of induction OR who did not receive augmented induction and/or consolidation (regardless of early marrow status) receive cranial irradiation. * Arm I: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising oral DM twice daily on days 0-4 and 28-32; VCR IV on days 0 and 28; oral MTX on days 0, 7, 14, 21, 28, 35, 42, and 49; oral MP on days 0-49; and MTX IT on day 28. Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV and doxorubicin (DOX) IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on day 3; cyclophosphamide (CTX) IV over 20-30 minutes on day 28; oral thioguanine (TG) on days 28-41; ARA-C IV or subcutaneously (SC) daily on days 28-31 and 35-38; and MTX IT on days 0 and 28. Beginning on day 56 of delayed intensification chemotherapy, patients receive interim maintenance II chemotherapy identical to interim maintenance I chemotherapy except patients receive MTX IT on days 0 and 28. Beginning on day 56 of interim maintenance II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0. * Arm II: Patients receive interim maintenance I chemotherapy, delayed intensification chemotherapy, and interim maintenance II chemotherapy as in arm I. Beginning on day 56 of interim maintenance II chemotherapy, patients then receive a second course of delayed intensification chemotherapy followed by maintenance chemotherapy as in arm I. * Arm III: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV; escalating doses of MTX IV on days 0, 10, 20, 30, and 40; and MTX IT on day 30. Patients then receive delayed intensification chemotherapy as in arm I. Patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the maximum tolerated dose (MTD) attained in interim maintenance I chemotherapy. Patients then receive maintenance chemotherapy as in arm I. * Arm IV: Patients receive interim maintenance I chemotherapy as in arm III, delayed intensification chemotherapy as in arm I, interim maintenance II chemotherapy as in arm III, delayed intensification II chemotherapy as in arm II, and maintenance chemotherapy as in arm I. * Augmented Treatment: Patients receive induction chemotherapy comprising daunorubicin IV continuously for 48 hours beginning no later than day 21; oral DM twice daily on days 14-27; and VCR IV on days 14 and 21. Patients without CNS disease at diagnosis receive MTX IT on days 21 and 35. Patients with CNS disease at diagnosis receive MTX IT on days 21 and 28. NOTE: Patients with T-cell disease should re-start with augmented consolidation and proceed as per the augmented regimen. Beginning on day 35 of induction chemotherapy, patients receive consolidation therapy comprising CTX IV over 20-30 minutes on days 0 and 28; oral MP on days 0-13 and 28-41; ARA-C IV or SC daily on days 0-3, 7-10, 28-31, and 35-38; VCR IV on days 14, 21, 42, and 49; and PEG-ASP IM on days 14 and 42. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, and 21. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation as in the randomized treatment section. Patients with testicular leukemia receive radiotherapy as in the randomized treatment section. Beginning on day 63 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV on days 0, 10, 20, 30, and 40; escalating doses of MTX IV on days 10, 20, 30, and 40; PEG-ASP IM on days 1 and 21; and MTX IT on days 0 and 30. Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification I chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV on days 0, 7, 14, 42, and 49; DOX IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on days 3 and 42; CTX IV over 20-30 minutes on day 28; oral TG on days 28-41; ARA-C IV or SC daily on days 28-31 and 35-38; and MTX IT on days 0 and 28. NOTE: Patients with T-cell disease who are in interim maintenance I chemotherapy with escalating IV methotrexate should continue this phase and then proceed as per the augmented regimen. If these patients are receiving conventional interim maintenance chemotherapy with oral methotrexate, they should stop and restart the interim maintenance as per the augmented regimen. These patients receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy. Beginning on day 56 of delayed intensification I chemotherapy, patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the MTD attained in interim maintenance I chemotherapy. NOTE: Patients with T-cell disease who are in delayed intensification I chemotherapy proceed with this phase, with the addition of 2 vincristine doses on days 42 and 49 and PEG-ASP on day 42. These patients then proceed as per the augmented regimen with the addition of cranial irradiation starting on day 28 of delayed intensification II chemotherapy. NOTE: Patients with T-cell disease who are within 4 months of completing delayed intensification I chemotherapy and have not received interim maintenance II chemotherapy with escalating IV methotrexate or delayed intensification II chemotherapy receive a course of interim maintenance chemotherapy and delayed intensification II chemotherapy according to the augmented regimen. If these patients have received interim maintenance II chemotherapy with escalating IV methotrexate, they receive delayed intensification II chemotherapy according to the augmented regimen. These patients also receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy and then proceed to maintenance therapy. Beginning on day 56 of interim maintenance II chemotherapy, patients receive delayed intensification II chemotherapy as in delayed intensification I chemotherapy. Beginning on day 56 of delayed intensification II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0. Patients are followed every 4-8 weeks for one year, every 3 months for one year, every 6 months for one year, and then annually thereafter. PROJECTED ACCRUAL: A total of 2,037 randomized patients will be accrued for this study within 3.75 years.
Source references
references
  1. citation
    Bruggers CS, Moyer-Mileur LJ, Ransdall L: Body composition, bone mineral acquisition, and cardiovascular fitness in children with standard risk acute lymphoblastic leukemia: response to a home-based exercise and nutrition education program. [Abstract] 2006 Pediatric Academic Societies' Annual Meeting, April 29 - May 2, San Francisco, CA. A-3505.46, 2006.
    type
    BACKGROUND
  2. citation
    Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.
    type
    BACKGROUND
  3. citation
    Fernandez CV, Kodish E, Taweel S, Shurin S, Weijer C; Children's Oncology Group. Disclosure of the right of research participants to receive research results: an analysis of consent forms in the Children's Oncology Group. Cancer. 2003 Jun 1;97(11):2904-9. doi: 10.1002/cncr.11391.
    pmid
    12767106
    type
    BACKGROUND
  4. citation
    Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. doi: 10.1182/blood-2010-12-322909. Epub 2011 May 11.
    pmid
    21562038
    type
    RESULT
  5. citation
    Matloub Y, Bostrom BC, Angiolillo AL, et al.: Children with NCI standard risk acute lymphoblastic leukemia (ALL) and TEL-AML1 or favorable chromosome trisomies are almost certain to be cured with graduated intensity therapy: results of the CCG - 1991 study. [Abstract] Blood 114 (22): A-320, 2009.
    type
    RESULT
  6. citation
    Matloub Y, Bostrom BC, Hunger SP, et al.: Escalating dose intravenous methotrexate without leucovorin rescue during interim maintenance is superior to oral methotrexate for children with standard risk acute lymphoblastic leukemia (SR-ALL): Children's Oncology Group study 1991. [Abstract] Blood 112 (11): A-9, 2008.
    type
    RESULT
  7. citation
    Matloub Y, Angiolillo A, Bostrom B, et al.: Double delayed intensification (DDI) is equivalent to single DI (SDI) in children with National Cancer Institute (NCI) standard-risk acute lymphoblastic leukemia (SR-ALL) treated on Children's Cancer Group (CCG) clinical trial 1991 (CCG-1991). [Abstract] Blood 108 (11): A-146, 2006.
    type
    RESULT
  8. citation
    Matloub Y, Rabin KR, Ji L, Devidas M, Hitzler J, Xu X, Bostrom BC, Stork LC, Winick N, Gastier-Foster JM, Heerema NA, Stonerock E, Carroll WL, Hunger SP, Gaynon PS. Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children's Oncology Group. Blood Adv. 2019 Jun 11;3(11):1647-1656. doi: 10.1182/bloodadvances.2019032094.
    pmid
    31160295
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        a href="#cit/section_7.71">71</a>,<a href="#cit/section_7.74">74</a>]</li><li>The former Children's Cancer Group (CCG) study (CCG-1991/<a href="/clinicaltrials/NCT00005945">COG-1991</a>) for standard-risk ALL used dexamethasone in a three-drug induction phase and tested the utility of a second delayed intensification phase. Thi
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        561678
        exact text
        NCT00005945
        start
        561667
      2. context exact
        the rate of CNS relapse compared with oral prednisone.[<a href="#cit/section_8.8">8</a>]</li><li> In another standard-risk ALL trial (<a href="/clinicaltrials/NCT00005945">COG-1991</a>), escalating dose IV methotrexate without leucovorin rescue significantly reduced the CNS relapse rate compared with standard, low-dose, oral met
        end
        700756
        exact text
        NCT00005945
        start
        700745
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        _9.5">5</a>] </li><li>Among children with NCI standard-risk T-ALL treated on the <a href="/clinicaltrials/NCT00002744">CCG-1952</a>, <a href="/clinicaltrials/NCT00005945">COG-1991</a>, and POG-9404 trials, the 7-year EFS rates were comparable with those of patients treated with the CCG regimens that used significantly less ant
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        769944
        exact text
        NCT00005945
        start
        769933
      4. context exact
        7; 1.9%], <em>P</em> = .817; OS rates, 86.7% [&#177; 6.7%] vs. 85.4% [&#177; 1.5%]; <em>P</em> = .852).</li></ul></div></li><li>In the <a href="/clinicaltrials/NCT00005945">CCG-1991 (NCT00005945)</a> study for children with standard-risk B-ALL (2000&#8211;2005), patients (including those with Down syndrome) were randomly assigned
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        821863
        exact text
        NCT00005945
        start
        821852
      5. context exact
        .817; OS rates, 86.7% [&#177; 6.7%] vs. 85.4% [&#177; 1.5%]; <em>P</em> = .852).</li></ul></div></li><li>In the <a href="/clinicaltrials/NCT00005945">CCG-1991 (NCT00005945)</a> study for children with standard-risk B-ALL (2000&#8211;2005), patients (including those with Down syndrome) were randomly assigned to receive an interim
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        821886
        exact text
        NCT00005945
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        Updated: April 21, 2025
        datetime
        2025-04-21T12:00:00Z
        display
        April 21, 2025

    Preserved source evidence · Not medical advice