Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk 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:	NCT00075725

Purpose

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in 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 acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia.

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	High Risk B-Precursor Acute Lymphoblastic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Calcium Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Dexamethasone Cyclophosphamide 6-Mercaptopurine Prednisone Vincristine Leucovorin Methotrexate Cytarabine hydrochloride Daunorubicin Doxorubicin Daunorubicin hydrochloride 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:

Improvement of the treatment outcome [ Designated as safety issue: No ]

Secondary Outcome Measures:

Relative safety and efficacy [ Designated as safety issue: Yes ]
Correlation of minimal residual disease (MRD) with event-free survival 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 with MRD at day 29 [ Designated as safety issue: No ]

Estimated Enrollment:	2964
Study Start Date:	December 2003
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.	Drug: cyclophosphamide Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: cytarabine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: daunorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: dexamethasone Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: doxorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: leucovorin calcium Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: mercaptopurine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: methotrexate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: pegaspargase Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: thioguanine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: vincristine sulfate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Radiation: radiation therapy Patients undergo radiation therapy periodically during study treatment
Active Comparator: Arm II Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1.	Drug: cyclophosphamide Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: cytarabine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: daunorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: dexamethasone Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: doxorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: leucovorin calcium Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: mercaptopurine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: methotrexate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: pegaspargase Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: thioguanine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: vincristine sulfate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Radiation: radiation therapy Patients undergo radiation therapy periodically during study treatment
Experimental: Arm III Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks.	Drug: cyclophosphamide Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: cytarabine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: daunorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: dexamethasone Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: doxorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: leucovorin calcium Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: mercaptopurine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: methotrexate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: pegaspargase Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: prednisone Given IV or orally Drug: thioguanine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: vincristine sulfate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Radiation: radiation therapy Patients undergo radiation therapy periodically during study treatment
Experimental: Arm IV Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks.	Drug: cyclophosphamide Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: cytarabine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: daunorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: dexamethasone Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: doxorubicin hydrochloride Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: leucovorin calcium Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: mercaptopurine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: methotrexate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: pegaspargase Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: prednisone Given IV or orally Drug: thioguanine Given IV, orally, intrathecally, intramuscularly, or subcutaneously Drug: vincristine sulfate Given IV, orally, intrathecally, intramuscularly, or subcutaneously Radiation: radiation therapy Patients undergo radiation therapy periodically during study treatment

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Eligibility

Ages Eligible for Study:	1 Year to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Newly diagnosed B-precursor acute lymphoblastic leukemia
- WBC > 50,000/mm^3 for patients age 1 to 9
- Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
Must be eligible for and enrolled on classification study COG-AALL03B1

PATIENT CHARACTERISTICS:

Age

1 to under 31

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Not specified

Renal

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No more than 72 hours since prior intrathecal cytarabine
No other prior cytotoxic chemotherapy

Endocrine therapy

Prior steroids allowed

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075725

Show 213 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Eric C. Larsen, MD

Maine Children's Cancer Program at Barbara Bush Children's Hospital

More Information

Additional Information:

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

Publications:

Raetz EA, Devidas M, Carroll AJ, et al.: Cytogenetic and early-response characteristics of adolescents and young adults with acute lymphoblastic leukemia (ALL): A Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9509, 2010.

Mattano LA Jr, Nachman JB, Devidas M, et al.: Increased incidence of osteonecrosis (ON) with a dexamethasone (DEX) induction for high risk acute lymphoblastic leukemia (HR-ALL): a report from the Children's Oncology Group (COG). [Abstract] Blood 112 (11): A-898, 2008.

Bleyer A: Older adolescents and young adults with acute lymphoblastic leukemia (ALL) in the United States: from the lowest to highest death rate and number of deaths--more rationale for the CALBG-SWOG-ECOG C10403 trial based on COG AALL0232. [Abstract] J Clin Oncol 26 (Suppl 15): A-18034, 2008.

Harvey RC, Chen IM, Ar K, et al.: Identification of novel cluster groups in high-risk pediatric B-precursor acute lymphoblastic leukemia (HR-ALL) by gene expression profiling: correlation with clinical and outcome variables a Children's Oncology Group (COG) study. [Abstract] Blood 112 (11): A-2256, 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:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT00075725 History of Changes
Other Study ID Numbers:	CDR0000349182, COG-AALL0232
Study First Received:	January 9, 2004
Last Updated:	January 20, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Pegaspargase

Daunorubicin
Dexamethasone
Doxorubicin
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 12, 2012