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Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002812
Recruitment Status : Completed
First Posted : November 24, 2003
Last Update Posted : August 26, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

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 or disease Intervention/treatment 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

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2078 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features: A Phase III Group-wide Study
Study Start Date : September 1996
Actual Primary Completion Date : March 2006


Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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. ]
    The primary outcome index used in examining most of the randomized treatment groups will be event-free survival (EFS).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002812


Locations
Show Show 35 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Nita L. Seibel, MD Children's National Research Institute
Publications of Results:
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.

Other Publications:
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002812    
Other Study ID Numbers: 1961
CCG-1961 ( Other Identifier: Children's Cancer Group )
CDR0000064953 ( Other Identifier: Clinical Trials.gov )
First Posted: November 24, 2003    Key Record Dates
Last Update Posted: August 26, 2013
Last Verified: August 2013
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:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Daunorubicin
Asparaginase
Mercaptopurine
Idarubicin
Pegaspargase
Thioguanine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action