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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00103285
First received: February 7, 2005
Last updated: April 21, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
B-cell Childhood Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: doxorubicin hydrochloride
Radiation: 3-dimensional conformal radiation therapy
Drug: cytarabine
Drug: dexamethasone
Drug: pegaspargase
Drug: methotrexate
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: cyclophosphamide
Drug: thioguanine
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival (EFS) for SR-average patients [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    All power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha = 0.05) with four planned analyses of the data for interim monitoring purposes. The 95% confidence interval for EFS for standard risk-high will also be computed.


Secondary Outcome Measures:
  • Health-related quality of life [ Time Frame: Up to 24 months after completion of all therapy ] [ Designated as safety issue: No ]
    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.

  • Correlation of minimal residual disease (MRD) with EFS [ Time Frame: At day 29 ] [ Designated as safety issue: No ]
    Cox regression will be utilized to examine the correlation between MRD levels and outcome (EFS).

  • Correlation of minimal residual disease (MRD) and overall survival [ Time Frame: At day 29 ] [ Designated as safety issue: No ]
    Cox regression will be utilized to examine the correlation between MRD levels and outcome (Overall Survival).

  • Correlation of early marrow response status with MRD [ Time Frame: At day 29 ] [ Designated as safety issue: No ]

Enrollment: 5377
Study Start Date: April 2005
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1 (SR-low ALL), Arm I (combination chemotherapy)
Patients receive Part I therapy. Patients then 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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Experimental: Group 1 (SR-low ALL), arm II (combination chemotherapy)
Patients receive Part I therapy. Patients then receive experimental consolidation therapy (vincristine sulfate, mercaptopurine, methotrexate, leucovorin calcium and pegaspargase), experimental interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine, methotrexate and pegaspargase), and standard DI therapy (vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, cyclophosphamide, cytarabine, thioguanine and methotrexate), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Active Comparator: Group 2 (SR-average ALL), arm I (combination chemotherapy)
Patients receive Part I therapy. Patients then 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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Experimental: Group 2 (SR-average ALL), arm II (combination chemotherapy)
Patients receive Part I therapy. Patients then receive standard consolidation therapy (vincristine sulfate, mercaptopurine and methotrexate. Patients with Down syndrome (DS) receive leucovorin calcium), augmented interim maintenance therapy (vincristine sulfate, methotrexate and pegaspargase. Patients with DS receive leucovorin calcium), augmented DI therapy (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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Active Comparator: Group 2 (SR-average ALL), arm III (combination chemotherapy)
Patients receive Part I therapy. Patients then receive intensified consolidation therapy (cyclophosphamide, cytarabine, mercaptopurine and vincristine sulfate, pegaspargase, methotrexate. Patients with DS receive oral leucovorin calcium), standard interim maintenance therapy (vincristine sulfate, dexamethasone, mercaptopurine and methotrexate. Patients with DS receive leucovorin calcium), and standard 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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Active Comparator: Group 2 (SR-average ALL), arm IV (combination chemotherapy)
Patients receive Part I therapy. Patients then receive intensified consolidation therapy (cyclophosphamide, cytarabine, mercaptopurine and vincristine sulfate, pegaspargase, methotrexate. Patients with DS receive oral leucovorin calcium), augmented interim maintenance therapy (vincristine sulfate, methotrexate and pegaspargase. Patients with DS receive leucovorin calcium), and augmented DI therapy (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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Experimental: Group 3 (SR-high ALL), combination chemotherapy
Patients receive Part I therapy. Patients then 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.
Drug: doxorubicin hydrochloride
Given IV or IT
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Radiation: 3-dimensional conformal radiation therapy
Some patients undergo cranial radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cytarabine
Given IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IM or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103285

  Show 224 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Kelly Maloney, MD Children's Oncology Group
  More Information

Publications:
Buchanan N, Maloney K, Tsang S, et al.: Risk of depression, anxiety, and somatization one month after diagnosis in children with standard risk ALL on COG AALL0331. [Abstract] J Clin Oncol 26 (Suppl 15): A-10052, 2008.
Stork LC, Buchanan N, Maloney K, et al.: Impairments in social and adaptive functioning one month after diagnosis in children with standard risk ALL on COG AALL0331. [Abstract] J Clin Oncol 26 (Suppl 15): A-10034, 2008.
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00103285     History of Changes
Other Study ID Numbers: AALL0331, NCI-2009-00302, COG-AALL0331, CDR0000409589, AALL0331, AALL0331, U10CA098543
Study First Received: February 7, 2005
Last Updated: April 21, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
6-Mercaptopurine
Asparaginase
BB 1101
Cyclophosphamide
Cytarabine
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Leucovorin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Pegaspargase
Thioguanine
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 29, 2015