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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00002812
Registration number
NCT00002812
Ethics application status
Date submitted
1/11/1999
Date registered
24/11/2003
Date last updated
26/08/2013
Titles & IDs
Public title
Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia
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Scientific title
Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features: A Phase III Group-wide Study
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Secondary ID [1]
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CCG-1961
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Secondary ID [2]
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1961
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Leukemia
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - asparaginase
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - cytarabine
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - dexamethasone
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - idarubicin
Treatment: Drugs - mercaptopurine
Treatment: Drugs - methotrexate
Treatment: Drugs - pegaspargase
Treatment: Drugs - prednisone
Treatment: Drugs - thioguanine
Treatment: Drugs - vincristine sulfate
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.
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.
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.
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.
Treatment: Drugs: asparaginase
Given IV
Treatment: Drugs: cyclophosphamide
Given IV
Treatment: Drugs: cytarabine
Given IV
Treatment: Drugs: daunorubicin hydrochloride
Given IV
Treatment: Drugs: dexamethasone
Given IV
Treatment: Drugs: doxorubicin hydrochloride
Given IV
Treatment: Drugs: idarubicin
Given IV
Treatment: Drugs: mercaptopurine
Given IV
Treatment: Drugs: methotrexate
Given PO
Treatment: Drugs: pegaspargase
Given IV
Treatment: Drugs: prednisone
Given PO
Treatment: Drugs: thioguanine
Given IV
Treatment: Drugs: vincristine sulfate
Given IV
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Event Free Survival
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Assessment method [1]
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The primary outcome index used in examining most of the randomized treatment groups will be event-free survival (EFS).
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Timepoint [1]
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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.
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Eligibility
Key inclusion 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
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Minimum age
1
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Maximum age
21
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/09/1996
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Date of last participant enrolment
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Date of last data collection
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Actual
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Sample size
Target
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Accrual to date
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Final
2078
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
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Princess Margaret Hospital for Children - Perth
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Recruitment postcode(s) [1]
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6001 - Perth
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Recruitment outside Australia
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United States of America
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California
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Colorado
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District of Columbia
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Illinois
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Indiana
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Iowa
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Michigan
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Wisconsin
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Canada
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British Columbia
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Canada
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Nova Scotia
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Funding & Sponsors
Primary sponsor type
Other
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Name
Children's Oncology Group
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Address
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Other collaborator category [1]
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Government body
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Name [1]
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National Cancer Institute (NCI)
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Ethics approval
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT00002812
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Trial related presentations / 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. doi: 10.1200/JCO.2006.07.7792. 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. doi: 10.2165/00003088-200544040-00003. 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. 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. doi: 10.1016/S1470-2045(12)70274-7. 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. doi: 10.1097/00043426-200404000-00002. 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. doi: 10.1182/blood-2007-02-070342. 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.
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Public notes
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Contacts
Principal investigator
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Nita L. Seibel, MD
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Children's National Research Institute
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Arce FJ, Seibel N, Gaynon PS, et al.: Pharmacokine...
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Avramis VI, Ettinger L, Martin-Aragon S, et al.: A...
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Avramis VI, Panosyan E, Avramis IA, et al.: Anti-a...
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Bhojwani D, Kang H, Menezes RX, Yang W, Sather H, ...
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Dhall G, Jones T, Radvinsky D, et al.: Adverse rea...
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Dhall G, Robison NJ, Rubin JI, et al.: Incidence o...
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Freyer DR, Devidas M, La M, Carroll WL, Gaynon PS,...
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Freyer DR, Seibel NL, La MK, et al.: Survival afte...
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Hastings C, Sather HN, Seibel NL, et al.: Outcomes...
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Hastings C, Whitlock JA, La M, et al.: Improved ou...
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Henze G. Early postinduction intensification thera...
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Mattano LA Jr, Devidas M, Nachman JB, Sather HN, H...
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Nachman JB, La MK, Hunger SP, Heerema NA, Gaynon P...
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Nachman J, Siebel N, Sather H, et al.: Outcome for...
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Panosyan EH, Grigoryan RS, Avramis IA, Seibel NL, ...
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Panosyan EH, Seibel NL, Grigoryan RS, et al.: Phar...
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Panosyan EH, Seibel NL, Martin-Aragon S, Gaynon PS...
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Seibel NL, Steinherz PG, Sather HN, Nachman JB, De...
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Withycombe JS, Post-White JE, Meza JL, Hawks RG, S...
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Results not provided in
https://clinicaltrials.gov/study/NCT00002812
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