Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00103285

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Standard Risk B-precursor Acute Lymphoblastic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Childhood

Drug Information available for: Dexamethasone Cyclophosphamide 6-Mercaptopurine Vincristine Leucovorin Methotrexate Cytarabine hydrochloride Doxorubicin Doxorubicin hydrochloride Citrovorum factor Dexamethasone acetate Doxiproct plus Pegaspargase Cytarabine Thioguanine Leucovorin Calcium Dexamethasone Sodium Phosphate Vincristine sulfate Folinic acid calcium salt pentahydrate Mercaptopurine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival (EFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Health-related quality of life [ Designated as safety issue: No ]
Correlation of minimal residual disease (MRD) with EFS and overall survival at day 29 [ Designated as safety issue: No ]
Correlation of early marrow response status with MRD at day 29 [ Designated as safety issue: No ]
Identification of additional high-risk patients by day 29 MRD [ Designated as safety issue: No ]
Contribution of genetic factors and early treatment response to outcome [ Designated as safety issue: No ]

Estimated Enrollment:	3381
Study Start Date:	January 2005
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 (SR-low ALL), arm I: Active Comparator Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 1 (SR-low ALL), arm II: Experimental Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 2 (SR-average ALL), arm I: Active Comparator Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 2 (SR-average ALL), arm II: Experimental Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 2 (SR-average ALL), arm III: Active Comparator Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 2 (SR-average ALL), arm IV: Active Comparator Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Group 3 (SR-high ALL): Experimental Patients receive Part I therapy. Patients then 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.	Drug: cyclophosphamide Given IV Drug: cytarabine Given intrathecally, IV, or subcutaneously Drug: dexamethasone Given IV or orally Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally Drug: mercaptopurine Given orally Drug: methotrexate Given IV, orally, or intrathecally Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo cranial radiotherapy

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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

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

Show 202 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Kelly Maloney, MD	Children's Hospital Center for Cancer and Blood Disorders
Investigator:	Leonard A. Mattano, MD	Bronson Methodist Hospital
Investigator:	Linda C. Stork, MD	Doernbecher Children's Hospital at Oregon Health & Science University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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.

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000409589, COG-AALL0331
Study First Received:	February 7, 2005
Last Updated:	February 6, 2010
ClinicalTrials.gov Identifier:	NCT00103285 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:

Dexamethasone
Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
6-Mercaptopurine
Hormones
Pegaspargase
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Hormonal
Thioguanine
Vincristine
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Doxorubicin
Neoplasms
Antineoplastic Agents, Phytogenic
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors

ClinicalTrials.gov processed this record on February 08, 2010