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: March 18, 2014
Last verified: March 2014
  Purpose

RATIONALE: 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.

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.


Condition Intervention Phase
Leukemia
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: thioguanine
Drug: vincristine sulfate
Radiation: radiation therapy
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

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 [ 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 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 (EFS).

  • Correlation of early marrow response status with MRD [ Time Frame: At day 29 ] [ Designated as safety issue: No ]
  • Identification of additional high-risk patients [ Time Frame: At Day 29 ] [ Designated as safety issue: No ]
  • Contribution of genetic factors and early treatment response to outcome [ Time Frame: At Day 29 ] [ Designated as safety issue: No ]

Enrollment: 5377
Study Start Date: January 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
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: Group 1 (SR-low ALL), arm II
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Active Comparator: Group 2 (SR-average ALL), arm I
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: Group 2 (SR-average ALL), arm II
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Active Comparator: Group 2 (SR-average ALL), arm III
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Active Comparator: Group 2 (SR-average ALL), arm IV
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: pegaspargase
Given intramuscularly
Other Names:
  • PEG-asparaginase
  • PEGLA
  • PEG-L-asparaginase
  • polyethylene glycol-L-asparaginase
  • Oncaspar
  • NSC #624239
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: Group 3 (SR-high ALL)
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: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: cytarabine
Given intrathecally, IV, or subcutaneously
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #63878
Drug: dexamethasone
Given IV or orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: leucovorin calcium
Given orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • 6-mercaptopurine
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • Trexall
  • NSC #000740
Drug: thioguanine
Given orally
Other Names:
  • 6-thioguanine
  • 2-amino-1
  • 7-dihydro-6H-purine-6-thione
  • WR-1141
  • Tabloid
  • Lanvis
  • NSC # 752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Some patients undergo cranial radiotherapy
Other Name: Augmented DI therapy: Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 9 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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
  • Concurrently enrolled on COG-AALL03B1

PATIENT CHARACTERISTICS:

Age

  • 1 to under 10

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Initial WBC < 50,000/mm^3

Hepatic

  • Not specified

Renal

  • Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior cytotoxic chemotherapy except intrathecal cytarabine

Endocrine therapy

  • Prior steroid therapy allowed at the discretion of the investigator
  • No contraindication to additional asparaginase therapy after induction for the standard risk-low study

Radiotherapy

  • No concurrent intensity-modulated radiotherapy

Surgery

  • Not specified
  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 199 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Kelly Maloney, MD Children's Hospital Colorado Center for Cancer and Blood Disorders
Study Chair: Leonard A. Mattano, MD Bronson Methodist Hospital
Study Chair: Linda C. Stork, MD Doernbecher Children's Hospital at Oregon Health and Science University
  More Information

Additional 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, COG-AALL0331, CDR0000409589
Study First Received: February 7, 2005
Last Updated: March 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia

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 October 29, 2014