Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia

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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

Study Description

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

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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.

Study Design

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Childhood Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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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

Contacts and Locations

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 35 study locations

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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
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
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

National Cancer Institute (NCI)

Investigators

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Study Chair:	Nita L. Seibel, MD	Children's National Research Institute

More Information

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.

Bhojwani D, Kang H, Menezes RX, Yang W, Sather H, Moskowitz NP, Min DJ, Potter JW, Harvey R, Hunger SP, Seibel N, Raetz EA, Pieters R, Horstmann MA, Relling MV, den Boer ML, Willman CL, Carroll WL; Children's Oncology Group Study; Dutch Childhood Oncology Group; German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia. Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected]. J Clin Oncol. 2008 Sep 20;26(27):4376-84. doi: 10.1200/JCO.2007.14.4519. Erratum in: J Clin Oncol. 2008 Nov 1;26(31):5142..

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, Devidas M, La M, Carroll WL, Gaynon PS, Hunger SP, Seibel NL. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group. Blood. 2011 Mar 17;117(11):3010-5. doi: 10.1182/blood-2010-07-294678. Epub 2010 Dec 30.

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.

Henze G. Early postinduction intensification therapy is essential in childhood acute lymphoblastic leukemia. Nat Clin Pract Oncol. 2008 Sep;5(9):502-3. doi: 10.1038/ncponc1184. Epub 2008 Jul 22.

Mattano LA Jr, Devidas M, Nachman JB, Sather HN, Hunger SP, Steinherz PG, Gaynon PS, Seibel NL; Children's Oncology Group. Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial. Lancet Oncol. 2012 Sep;13(9):906-15. Epub 2012 Aug 15.

Nachman JB, La MK, Hunger SP, Heerema NA, Gaynon PS, Hastings C, Mattano LA Jr, Sather H, Devidas M, Freyer DR, Steinherz PG, Seibel NL. Young adults with acute lymphoblastic leukemia have an excellent outcome with chemotherapy alone and benefit from intensive postinduction treatment: a report from the children's oncology group. J Clin Oncol. 2009 Nov 1;27(31):5189-94. doi: 10.1200/JCO.2008.20.8959. Epub 2009 Oct 5.

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, Grigoryan RS, Avramis IA, Seibel NL, Gaynon PS, Siegel SE, Fingert HJ, Avramis VI. Deamination of glutamine is a prerequisite for optimal asparagine deamination by asparaginases in vivo (CCG-1961). Anticancer Res. 2004 Mar-Apr;24(2C):1121-5.

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.

Panosyan EH, Seibel NL, Martin-Aragon S, Gaynon PS, Avramis IA, Sather H, Franklin J, Nachman J, Ettinger LJ, La M, Steinherz P, Cohen LJ, Siegel SE, Avramis VI; Children's Cancer Group Study CCG-1961. Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia: Children's Cancer Group Study CCG-1961. J Pediatr Hematol Oncol. 2004 Apr;26(4):217-26.

Seibel NL, Steinherz PG, Sather HN, Nachman JB, Delaat C, Ettinger LJ, Freyer DR, Mattano LA Jr, Hastings CA, Rubin CM, Bertolone K, Franklin JL, Heerema NA, Mitchell TL, Pyesmany AF, La MK, Edens C, Gaynon PS. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 1;111(5):2548-55. Epub 2007 Nov 26.

Withycombe JS, Post-White JE, Meza JL, Hawks RG, Smith LM, Sacks N, Seibel NL. Weight patterns in children with higher risk ALL: A report from the Children's Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer. 2009 Dec 15;53(7):1249-54. doi: 10.1002/pbc.22237.

Other Publications:

Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008 Dec;22(12):2142-50. doi: 10.1038/leu.2008.251. Epub 2008 Sep 25.

Butturini AM, Dorey FJ, Lange BJ, Henry DW, Gaynon PS, Fu C, Franklin J, Siegel SE, Seibel NL, Rogers PC, Sather H, Trigg M, Bleyer WA, Carroll WL. Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol. 2007 May 20;25(15):2063-9.

Avramis VI, Panosyan EH. Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: the past, the present and recommendations for the future. Clin Pharmacokinet. 2005;44(4):367-93. Review.

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.

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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:

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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

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