Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002812
First received: November 1, 1999
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different combinations may kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of standard combination chemotherapy treatment with more intensive combination chemotherapy in treating children with acute lymphocytic leukemia.


Condition Intervention Phase
Leukemia
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: idarubicin
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features: A Phase III Group-wide Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event Free Survival [ Time Frame: from the time of randomization where the life table events will consist of the first occurrence of the following events: failure to achieve remission, leukemic relapse at any site, death, or occurrence of a second malignancy. ] [ Designated as safety issue: No ]
    The primary outcome index used in examining most of the randomized treatment groups will be event-free survival (EFS).


Enrollment: 2078
Study Start Date: September 1996
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - Standard BFM of Standard Duration (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow. Consolidation (Phase II) (5 weeks) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
Radiation: radiation therapy
Experimental: Arm B - Standard BFM with Double Delayed Intensification (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (5 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
Radiation: radiation therapy
Experimental: Arm C - Augumented BFM of Standard Duration (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (9 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
Radiation: radiation therapy
Experimental: Arm D - Augmented BFM with Dbl Delayed Intensification (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (9 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
Radiation: radiation therapy

  Hide Detailed Description

Detailed Description:

OBJECTIVES: I. Compare the outcomes in children with higher risk acute lymphocytic leukemia (ALL) treated with postinduction chemotherapy based on marrow response on day 7 of induction therapy: for patients with rapid early response (M1/M2), standard vs intensified consolidation chemotherapy and standard vs prolonged duration of intensification chemotherapy; for patients with slow early response, addition of doxorubicin vs idarubicin and cyclophosphamide to intensification chemotherapy. II. Decrease the incidence of avascular necrosis by alternating dexamethasone dosing in patients undergoing 2 courses of delayed intensification. III. Assess the impact of day 7 marrow status on outcome in these patients. IV. Determine prognosis more precisely by supplementing presenting clinical features, immunophenotype, ploidy, cytogenetics, and early marrow response with BAX/BCL-2 ratios, pattern of tyrosine kinase activation, leukemic burden following induction and intensification therapy, and development of high antibody titer to E. coli asparaginase. V. Correlate the traditional prognostic factors of day 7 marrow response, immunophenotype, ploidy, cytogenetics, and early marrow response with BAX/BCL-2 ratios.

OUTLINE: This is a partially randomized, multicenter study. Patients are stratified by center. Patients receive one course of the VPLD regimen comprised of vincristine IV and daunorubicin IV over 15 minutes to 2 hours on days 0 and 7, oral prednisone daily on days 0-7, intrathecal cytarabine on day 0, and asparaginase or pegaspargase intramuscularly on days 3, 5, and 7. Patients are assigned to 1 of 2 two postinduction chemotherapy groups based on bone marrow response on day 7 of induction. Patients with M1/M2 marrow on day 7 are considered rapid early responders. Patients with M3 marrow on day 7 are considered slow early responders. Group 1: Rapid early responders Patients receive 2 additional courses of VPLD induction chemotherapy. Patients are then randomized to 1 of 4 treatment arms: Arm I: Beginning on day 35 of induction therapy, patients receive standard Berlin-Frankfurt-Munster (BFM) regimen with standard delayed intensification. Standard BFM for patients in arm I consists of the following: consolidation over 5 weeks with cyclophosphamide, cytarabine, and mercaptopurine; interim maintenance over 8 weeks with oral methotrexate and mercaptopurine (MTX/MP); and delayed intensification over 7 weeks consisting of reinduction with vincristine, doxorubicin, oral dexamethasone, and asparaginase or pegaspargase followed by reconsolidation with cyclophosphamide, thioguanine, and cytarabine. Arm II: Patients receive standard BFM regimen with double delayed intensification. Patients receive therapy similar to those in arm I, but dexamethasone is interrupted for 1 week during delayed intensification and the intensification regimen is repeated, separated by an 8 week interim maintenance course of oral MTX/MP. Arm III: Patients receive augmented BFM regimen with standard delayed intensification. Patients receive 9 weeks of consolidation therapy with 2 courses of vincristine and pegaspargase alternating with the arm I consolidation therapy. Vincristine, intravenous methotrexate, and pegaspargase (the Capizzi I regimen) are substituted for oral MTX/MP in the interim maintenance regimen. Pegaspargase is substituted for asparaginase and two additional doses of vincristine are administered during delayed intensification. Arm IV: Patients receive augmented BFM regimen with double delayed intensification. Patients receive intensified chemotherapy throughout, combining the additional therapy given to patients in arms II and III. Patients receiving augmented BFM regimen receive pegaspargase instead of asparaginase. Patients with CNS disease at diagnosis are treated only on arm IV. Patients who are Philadelphia chromosome positive and do not have a bone marrow donor are nonrandomly assigned to the treatment group for slow early responders. All RER patients receive the same maintenance therapy with vincristine/prednisone and oral MTX/MP. Intrathecal methotrexate is administered periodically throughout protocol treatment. Group 2: Slow early responders Patients receive augmented BFM consolidation therapy and Capizzi I interim maintenance identical to that received by rapid early responders in arm IV. Patients are then randomized to receive double delayed intensification with either idarubicin or doxorubicin and concurrent cyclophosphamide. All patients receive the same maintenance therapy with vincristine/prednisone and oral MTX/MP. Intrathecal MTX is administered periodically throughout protocol treatment. Patients with CNS disease at entry receive craniospinal irradiation daily for 5 consecutive days beginning on day 0 of consolidation therapy. All slow early responders at diagnosis receive cranial irradiation daily for 5 consecutive days during consolidation therapy. Patients with testicular leukemia at diagnosis receive bilateral testicular irradiation daily for 5 consecutive days during consolidation chemotherapy. Groups 1 and 2: Maintenance therapy continues for 2 years for girls or 3 years for boys beyond completion of consolidation therapy. Patients are followed every 4-6 weeks for 1 year, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1,520 patients will be accrued for this study over 4 years.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Acute lymphocytic leukemia (ALL) with M3 bone marrow No FAB L3 morphology CNS or overt testicular leukemia at diagnosis allowed High risk status 10-21 years old with any white blood count (WBC) 1-9 years old with WBC of 50,000/mm3 or greater

PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified

PRIOR CONCURRENT THERAPY: No prior therapy for ALL except: Emergency therapy for blast crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration Biologic therapy: Not specified Chemotherapy: Intrathecal cytarabine or methotrexate allowed at diagnostic lumbar puncture Induction therapy must begin within 72 hours after intrathecal injection Endocrine therapy: At least 1-2 months since prior prednisone, for less than 48 hours, for reactive airway disease Inhalational steroids allowed Radiotherapy: Not specified Surgery: Not specified

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002812

  Hide Study Locations
Locations
United States, California
Long Beach Memorial Medical Center
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Children's Hospital of Orange County
Orange, California, United States, 92868
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, Colorado
Children's Hospital of Denver
Denver, Colorado, United States, 80218
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Iowa
Holden Comprehensive Cancer Center at The University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0752
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3330
United States, New Jersey
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08901-1780
United States, New York
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, North Carolina
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, United States, 27599-7295
United States, Ohio
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45229-3039
Ireland Cancer Center
Cleveland, Ohio, United States, 44106-5065
Children's Hospital of Columbus
Columbus, Ohio, United States, 43205-2696
United States, Oregon
Doernbecher Children's Hospital
Portland, Oregon, United States, 97201-3098
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Nita L. Seibel, MD Children's Research Institute
  More Information

Additional Information:
Publications:
Arce FJ, Seibel N, Gaynon PS, et al.: Pharmacokinetics and pharmacodynamics of asparaginases in antibody-negative pediatric patients with higher risk acute lymphoblastic leukemia (ALL): a report from CCG-1961. [Abstract] J Clin Oncol 24 (Suppl 18): A-9027, 508s, 2006.
Avramis VI, Ettinger L, Martin-Aragon S, et al.: Anti-asparaginase (ASNase) antibody (Ab) in pediatric patients in high risk ALL study (CCG-1961): correlation of Ab and clinical allergy. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2319, 2000.
Avramis VI, Panosyan E, Avramis IA, et al.: Anti-asparaginase (ASNase) antibody (Ab) and ASNase activity in children with higher risk acute lymphoblastic leukemia (HR ALL) (CCG-1961). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1592, 2002.
Dhall G, Jones T, Radvinsky D, et al.: Adverse reactions to PEG and Erwinia asparaginase and correlation with anti-asparaginase antibody data and survival in children with acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group study CCG 1961. [Abstract] Blood 114 (22): A-3077, 2009.
Dhall G, Robison NJ, Rubin JI, et al.: Incidence of adverse reactions to post-induction asparaginase (ASP) therapy in children and adolescents with high-risk acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group Study CCG-1961. [Abstract] J Clin Oncol 26 (Suppl 15): A-10021, 2008.
Freyer DR, Seibel NL, La MK, et al.: Survival after relapse in higher risk acute lymphoblastic leukemia (ALL) in children and adolescents is independent of prior treatment intensity: a report from the Children's Oncology Group (COG). [Abstract] Blood 112 (11): A-917, 2008.
Hastings C, Sather HN, Seibel NL, et al.: Outcomes in children and adolescents with a markedly elevated white blood cell count (>200,000) at diagnosis of high risk acute lymphoblastic leukemia (ALL): a report from the Children's Oncology Group. [Abstract] Blood 108 (11): A-1870, 2006.
Hastings C, Whitlock JA, La M, et al.: Improved outcome of children with Down syndrome (DS) and high risk acute lymphocytic leukemia (HR-ALL): a report of CCG-1961. [Abstract] Blood 110 (11): A-586, 2007.
Nachman J, Siebel N, Sather H, et al.: Outcome for adolescent and young adults 16-21 years of age (AYA) with acute lymphoblastic leukemia (ALL) treated on the Children' s Cancer Group (CCG) 1961 study. [Abstract] Blood 104 (11): A-683, 2004.
Panosyan EH, Seibel NL, Grigoryan RS, et al.: Pharmacokinetics and pharmacodynamics of three asparaginases in pediatric patients with higher risk acute lymphoblastic leukemia: a report from CCG-1961. [Abstract] Blood 104 (11): A-2745, 2004.
Seibel NL, Asselin BL, Nachman JB, et al.: Treatment of high risk T-cell acute lymphoblastic leukemia (T-ALL): comparison of recent experience of the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG). [Abstract] Blood 104 (11): A-681, 2004.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002812     History of Changes
Other Study ID Numbers: 1961, CCG-1961, CDR0000064953
Study First Received: November 1, 1999
Last Updated: August 23, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood 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
Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Idarubicin
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 15, 2014