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NCT00002756 · CITED IN SOURCE DOCUMENTS

Induction Intensification in Treating Infants 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
PHASE2
Status at capture
COMPLETED
Registry last update
2014-02-14

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and giving them as induction intensification may kill more cancer cells. PURPOSE: This phase II trial is studying how well induction intensification works in treating infants with newly diagnosed acute lymphocytic 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: * Newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia * No infants less than 36 weeks' gestation * CNS or testicular disease permitted * No B-cell ALL or acute myeloid leukemia * Previously untreated except for the following: * Steroid treatment within 48 hours of diagnosis allowed with physical examination and differential CBC immediately prior to beginning steroids * Concurrent registration on protocol POG-9900 (ALL classification study) required * Patients registered on POG-9407 are eligible for the pharmacokinetic part of the study PATIENT CHARACTERISTICS: Age: * Under 1 at diagnosis Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified Other: * No uncontrolled infection * Adequate major organ function PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Not specified Endocrine therapy: * See Disease Characteristics * No concurrent chronic steroid treatment Radiotherapy: * Not specified Surgery: * Not specified Other: * No other concurrent anticancer therapy
healthy Volunteers
false
maximum Age
1 Year
sex
ALL
std Ages
  1. CHILD
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Biological: filgrastim
    2. Drug: asparaginase
    3. Drug: cyclophosphamide
    4. Drug: cytarabine
    5. Drug: daunorubicin hydrochloride
    6. Drug: etoposide
    7. Drug: leucovorin calcium
    8. Drug: mercaptopurine
    9. Drug: methotrexate
    10. Drug: prednisone
    11. Drug: therapeutic hydrocortisone
    12. Drug: vincristine sulfate
    label
    Chemo (Reduced Induction) No BMT (Open February 2004)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    filgrastim
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    asparaginase
    type
    DRUG
  3. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    cyclophosphamide
    type
    DRUG
  4. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    cytarabine
    type
    DRUG
  5. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    daunorubicin hydrochloride
    type
    DRUG
  6. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    etoposide
    type
    DRUG
  7. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    leucovorin calcium
    type
    DRUG
  8. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    mercaptopurine
    type
    DRUG
  9. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    methotrexate
    type
    DRUG
  10. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    prednisone
    type
    DRUG
  11. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    therapeutic hydrocortisone
    type
    DRUG
  12. arm Group Labels
    1. Chemo (Reduced Induction) No BMT (Open February 2004)
    name
    vincristine sulfate
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
221
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Feasibility of intensification
  2. measure
    Event-free survival
  3. measure
    Comparison of event-free survival rates in infants with and without leukemic blasts translocations
secondary Outcomes
  1. measure
    Correlation of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome
  2. measure
    Clinical prognostic features associated with outcome
  3. measure
    Correlation of biologic characteristics of leukemia cells at diagnosis with outcome
  4. measure
    Patterns of gene expression
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and giving them as induction intensification may kill more cancer cells. PURPOSE: This phase II trial is studying how well induction intensification works in treating infants with newly diagnosed acute lymphocytic leukemia.
detailed Description
OBJECTIVES: Primary * Assess the feasibility of intensification with two courses of high-dose methotrexate followed by one course of cyclophosphamide/etoposide during induction and later as consolidation in infants with newly diagnosed acute lymphoblastic leukemia. * Determine event-free survival after shortened, intensive therapy in these patients. * Compare event-free survival rates of infants receiving this regimen whose leukemic blasts have or do not have translocations involving the 11q23 gene MLL. Secondary * Correlate the presence of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome. * Investigate the clinical prognostic features that may be associated with outcome in infants, such as bone marrow blast content at day 8, white blood cell count, and age. * Correlate biologic characteristics of the leukemia cells at diagnosis (protocol POG-9900) with outcome in patients treated with this regimen. * Characterize patterns of gene expression associated with host and disease characteristics and treatment response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to participating center and presence of CNS disease (yes vs no). Patients receive induction chemotherapy comprising vincristine IV on days 1, 8, and 15; oral prednisone three times a day on days 1-21; daunorubicin IV over 30 minutes on days 1-2; cyclophosphamide IV over 30 minutes every 12 hours on days 3-4; and asparaginase intramuscularly (IM) on days 4, 6, 8, 10, 12, 15, 17, and 19. Patients also receive triple intrathecal therapy comprising methotrexate, hydrocortisone, and cytarabine on days 1, 8, and 15 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 5 and continuing until day 20, regardless of blood counts. Patients receive induction intensification chemotherapy comprising high-dose methotrexate IV over 24 hours; triple intrathecal therapy as per induction therapy on days 22 and 29; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 36-40. Patients receive G-CSF SC or IV beginning on day 41 and continuing until blood counts recover. Patients achieving morphologic remission and recovery of blood counts while off G-CSF for 48 hours receive reinduction chemotherapy comprising the same regimen as in induction therapy with the exception of asparaginase IM beginning on day 1 (week 8) and continuing every Monday, Wednesday, and Friday for a total of 8 doses and triple intrathecal therapy on days 1 and 15 only (weeks 8 and 10). Patients receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. After blood count recovery, patients receive consolidation chemotherapy comprising triple intrathecal therapy as per induction therapy on day 1 (week 11); high-dose methotrexate IV over 24 hours on weeks 8 and 12; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 15-19 (week 13). Patients receive G-CSF SC or IV beginning on day 20 and continuing until blood counts recover. On days 29-31 (week 15), patients receive high-dose cytarabine IV over 3 hours every 12 hours for 4 doses and asparaginase IM 6 hours after completion of high-dose cytarabine. Patients receive G-CSF beginning 24 hours after completion of asparaginase and continuing until blood counts recover. Patients achieving morphologic remission and blood count recovery while off G-CSF for 48 hours receive continuation therapy comprising vincristine IV on day 1; oral prednisone three times a day on days 1-5; and triple intrathecal therapy on day 1 (weeks 18 and 22). Patients also receive methotrexate IM once a week and oral mercaptopurine daily on weeks 19-21, 23, and 24. On week 25, patients receive etoposide IV over 2 hours daily followed by cyclophosphamide IV over 30 minutes daily on days 1-5 and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Patients receive an additional course of continuation therapy on weeks 28-35. On weeks 38-48, patients receive another identical course of continuation therapy with the exclusion of the etoposide and cyclophosphamide combination regimen. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: Approximately 58-104 patients will be accrued for this study within 2.1 years.
Source references
references
  1. citation
    Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, Hilden JM, Heerema NA, Sanders JE, McGlennen R, Willman CL, Carroll AJ, Behm F, Smith FO, Woods WG, Godder K, Reaman GH. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group. J Clin Oncol. 2011 Jan 10;29(2):214-22. doi: 10.1200/JCO.2009.26.8938. Epub 2010 Dec 6.
    pmid
    21135279
    type
    BACKGROUND
  2. 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
  3. citation
    Kang H, Wilson CS, Harvey RC, Chen IM, Murphy MH, Atlas SR, Bedrick EJ, Devidas M, Carroll AJ, Robinson BW, Stam RW, Valsecchi MG, Pieters R, Heerema NA, Hilden JM, Felix CA, Reaman GH, Camitta B, Winick N, Carroll WL, Dreyer ZE, Hunger SP, Willman CL. Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2012 Feb 23;119(8):1872-81. doi: 10.1182/blood-2011-10-382861. Epub 2011 Dec 30.
    pmid
    22210879
    type
    RESULT
  4. citation
    Salzer WL, Jones TL, Devidas M, Hilden JM, Winick N, Hunger S, Carroll WL, Camitta B, Dreyer ZE. Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407. Pediatr Blood Cancer. 2012 Nov;59(5):834-9. doi: 10.1002/pbc.24132. Epub 2012 Apr 5.
    pmid
    22488662
    type
    RESULT
  5. citation
    Robinson BW, Devidas M, Carroll AJ, et al.: Specific MLL partner genes in infant acute lymphoblastic leukemia (ALL) associated with outcome are linked to age and white blood cell count (WBC) at diagnosis: A report on the Children's Oncology Group (COG) P9407 trial. [Abstract] Blood 114 (22): A-907, 2009.
    type
    RESULT
  6. citation
    Thompson PA, Murry DJ, Rosner GL, Lunagomez S, Blaney SM, Berg SL, Camitta BM, Dreyer ZE, Bomgaars LR. Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2007 May;59(6):847-53. doi: 10.1007/s00280-006-0388-1. Epub 2006 Nov 29.
    pmid
    17136402
    type
    RESULT
Source notices and limitations
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        le outcome with the cytarabine-intensive treatment regimen (4-year EFS rate, 74%).[<a href="#cit/section_9.23">23</a>]</li><li>The COG <a href="/clinicaltrials/NCT00002756">P9407 (NCT00002756)</a> trial of intensified chemotherapy reported a 5-year EFS rate of 70% in infants without the <em class="gene-name">KMT2A</em> rearrangem
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        cytarabine-intensive treatment regimen (4-year EFS rate, 74%).[<a href="#cit/section_9.23">23</a>]</li><li>The COG <a href="/clinicaltrials/NCT00002756">P9407 (NCT00002756)</a> trial of intensified chemotherapy reported a 5-year EFS rate of 70% in infants without the <em class="gene-name">KMT2A</em> rearrangement.[<a href="#cit/s
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      1. context
        Updated: April 21, 2025
        datetime
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        display
        April 21, 2025

    Preserved source evidence · Not medical advice