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

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 Procedure: radiation therapy	Phase III

MedlinePlus related topics:

Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for:

Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Cytarabine Cytarabine hydrochloride Mercaptopurine 6-Mercaptopurine Daunorubicin hydrochloride Daunorubicin Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Prednisone Vincristine sulfate Vincristine Calcium gluconate Thioguanine Pegaspargase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control

Official Title:	High Risk B-Precursor Acute Lymphoblastic Leukemia

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
Arm I: Active Comparator 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 Procedure: radiation therapy Patients undergo radiation therapy periodically during study treatment
Arm II: Active Comparator 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 Procedure: radiation therapy Patients undergo radiation therapy periodically during study treatment
Arm III: Experimental 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 Procedure: radiation therapy Patients undergo radiation therapy periodically during study treatment
Arm IV: Experimental 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 Procedure: 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 195 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

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

Publications:

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.

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.

Study ID Numbers:	CDR0000349182, COG-AALL0232
First Received:	January 9, 2004
Last Updated:	November 11, 2008
ClinicalTrials.gov Identifier:	NCT00075725
Health Authority:	Unspecified

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

Study placed in the following topic categories:

Dexamethasone

Prednisone

Daunorubicin

Leukemia, Lymphoid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Immunoproliferative Disorders

Thioguanine

Vincristine

Leucovorin

6-Mercaptopurine

Cyclophosphamide

Doxorubicin

Acute lymphoblastic leukemia, adult

Folic Acid

Pegaspargase

Leukemia

Lymphatic Diseases

Methotrexate

Lymphoproliferative Disorders

Lymphoma

Cytarabine

Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents

Antimetabolites

Anti-Infective Agents

Antimetabolites, Antineoplastic

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists

Antiemetics

Reproductive Control Agents

Antibiotics, Antineoplastic

Hormones

Vitamins

Therapeutic Uses

Abortifacient Agents

Micronutrients

Dermatologic Agents

Alkylating Agents

Nucleic Acid Synthesis Inhibitors

Vitamin B Complex

Neoplasms by Histologic Type

Antineoplastic Agents, Hormonal

Immune System Diseases

Growth Substances

Mitosis Modulators

Gastrointestinal Agents

Enzyme Inhibitors

Antimitotic Agents

Folic Acid Antagonists

ClinicalTrials.gov processed this record on November 19, 2008

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00075725