Total Therapy Study XIV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

NCT00187005 | Terminated Phase 3 DMC

• 1 other identifier: TOTXIV
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to find out if radiation to the central nervous system (CNS) can be safely omitted with early intensification of chemotherapy and chemotherapy given directly to the CNS. Another purpose is to find out if survival of children with ALL can be improved with risk-directed therapy given on this protocol.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Leukemia

Outcome Measures

Primary Outcomes (1)

• To determine if CNS irradiation can be safely omitted with early intensification of systemic and intrathecal chemotherapy.

  Unable to determine

Study Arms (1)

1

OTHER

Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin, PEG-L-asparaginase; Drug: L-asparaginase, Methotrexate, Idarubicin, Etoposide, Cyclophosphamide, Cytarabine, Mercaptopurine

Interventions

Prednisone, Dexamethasone, Vincristine, Daunorubicin, PEG-L-asparaginase DRUG

See Detailed Description section for details of treatment interventions.

1

L-asparaginase, Methotrexate, Idarubicin, Etoposide, Cyclophosphamide, Cytarabine, Mercaptopurine DRUG

See Detailed Description section for details of treatment interventions.

1

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of non-B-cell leukemia by immunophenotyping (e.g. T-cell, B-cell precursor, or acute undifferentiated leukemia)
• Ages less than or equal to 18 years of age

You may not qualify if:

• Participants greater than 18 years of age

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St.Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (31)

• Hammond TG, Hu A, Hammond JM, Relling MV, Underwood JL. Detection of point mutations on a DNA microchip Clinical Immunology Newsletter 19(12):121-6, 1999.

  BACKGROUND

• Pui CH, Mahmoud HH, Wiley JM, Woods GM, Leverger G, Camitta B, Hastings C, Blaney SM, Relling MV, Reaman GH. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. J Clin Oncol. 2001 Feb 1;19(3):697-704. doi: 10.1200/JCO.2001.19.3.697.

  PMID: 11157020 BACKGROUND

• Pui CH, Jeha S, Irwin D, Camitta B. Recombinant urate oxidase (rasburicase) in the prevention and treatment of malignancy-associated hyperuricemia in pediatric and adult patients: results of a compassionate-use trial. Leukemia. 2001 Oct;15(10):1505-9. doi: 10.1038/sj.leu.2402235.

  PMID: 11587206 BACKGROUND

• Panetta JC, Yanishevski Y, Pui CH, Sandlund JT, Rubnitz J, Rivera GK, Ribeiro R, Evans WE, Relling MV. A mathematical model of in vivo methotrexate accumulation in acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2002 Nov;50(5):419-28. doi: 10.1007/s00280-002-0511-x. Epub 2002 Sep 24.

  PMID: 12439601 BACKGROUND

• Coustan-Smith E, Sancho J, Behm FG, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, Pui CH, Campana D. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood. 2002 Jul 1;100(1):52-8. doi: 10.1182/blood-2002-01-0006.

  PMID: 12070008 BACKGROUND

• Coustan-Smith E, Sancho J, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, Pui CH, Campana D. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood. 2002 Oct 1;100(7):2399-402. doi: 10.1182/blood-2002-04-1130.

  PMID: 12239148 BACKGROUND

• Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002 Mar;1(2):133-43. doi: 10.1016/s1535-6108(02)00032-6.

  PMID: 12086872 BACKGROUND

• Panetta JC, Wall A, Pui CH, Relling MV, Evans WE. Methotrexate intracellular disposition in acute lymphoblastic leukemia: a mathematical model of gamma-glutamyl hydrolase activity. Clin Cancer Res. 2002 Jul;8(7):2423-9.

  PMID: 12114448 BACKGROUND

• Cheok MH, Yang W, Pui CH, Downing JR, Cheng C, Naeve CW, Relling MV, Evans WE. Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells. Nat Genet. 2003 May;34(1):85-90. doi: 10.1038/ng1151.

  PMID: 12704389 BACKGROUND

• Kishi S, Griener J, Cheng C, Das S, Cook EH, Pei D, Hudson M, Rubnitz J, Sandlund JT, Pui CH, Relling MV. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J Clin Oncol. 2003 Aug 15;21(16):3084-91. doi: 10.1200/JCO.2003.07.056.

  PMID: 12915598 BACKGROUND

• Hinds PS, Gattuso JS, Fletcher A, Baker E, Coleman B, Jackson T, Jacobs-Levine A, June D, Rai SN, Lensing S, Pui CH. Quality of life as conveyed by pediatric patients with cancer. Qual Life Res. 2004 May;13(4):761-72. doi: 10.1023/B:QURE.0000021697.43165.87.

  PMID: 15129886 BACKGROUND

• Hak LJ, Relling MV, Cheng C, Pei D, Wang B, Sandlund JT, Rubnitz J, Pui CH. Asparaginase pharmacodynamics differ by formulation among children with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2004 Jun;18(6):1072-7. doi: 10.1038/sj.leu.2403351.

  PMID: 15057247 BACKGROUND

• Neale GA, Coustan-Smith E, Stow P, Pan Q, Chen X, Pui CH, Campana D. Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia. 2004 May;18(5):934-8. doi: 10.1038/sj.leu.2403348.

  PMID: 15029212 BACKGROUND

• Cheng Q, Wu B, Kager L, Panetta JC, Zheng J, Pui CH, Relling MV, Evans WE. A substrate specific functional polymorphism of human gamma-glutamyl hydrolase alters catalytic activity and methotrexate polyglutamate accumulation in acute lymphoblastic leukaemia cells. Pharmacogenetics. 2004 Aug;14(8):557-67. doi: 10.1097/01.fpc.0000114761.78957.7e.

  PMID: 15284538 BACKGROUND

• Rubnitz JE, Lensing S, Zhou Y, Sandlund JT, Razzouk BI, Ribeiro RC, Pui CH. Death during induction therapy and first remission of acute leukemia in childhood: the St. Jude experience. Cancer. 2004 Oct 1;101(7):1677-84. doi: 10.1002/cncr.20532.

  PMID: 15378506 BACKGROUND

• Glass JO, Reddick WE, Reeves C, Pui CH. Improving the segmentation of therapy-induced leukoencephalopathy in children with acute lymphoblastic leukemia using a priori information and a gradient magnitude threshold. Magn Reson Med. 2004 Dec;52(6):1336-41. doi: 10.1002/mrm.20259.

  PMID: 15562471 BACKGROUND

• Cox CL, Lensing S, Rai SN, Hinds P, Burghen E, Pui CH. Proxy assessment of quality of life in pediatric clinical trials: application of the Health Utilities Index 3. Qual Life Res. 2005 May;14(4):1045-56. doi: 10.1007/s11136-004-4714-y.

  PMID: 16041900 BACKGROUND

• Reddick WE, Glass JO, Helton KJ, Langston JW, Xiong X, Wu S, Pui CH. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol. 2005 May;26(5):1263-9.

  PMID: 15891195 BACKGROUND

• Lowe EJ, Pui CH, Hancock ML, Geiger TL, Khan RB, Sandlund JT. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005 Jul;45(1):10-5. doi: 10.1002/pbc.20178.

  PMID: 15547931 BACKGROUND

• Cheng Q, Yang W, Raimondi SC, Pui CH, Relling MV, Evans WE. Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes. Nat Genet. 2005 Aug;37(8):878-82. doi: 10.1038/ng1612. Epub 2005 Jul 24.

  PMID: 16041371 BACKGROUND

• Zaza G, Cheok M, Yang W, Panetta JC, Pui CH, Relling MV, Evans WE. Gene expression and thioguanine nucleotide disposition in acute lymphoblastic leukemia after in vivo mercaptopurine treatment. Blood. 2005 Sep 1;106(5):1778-85. doi: 10.1182/blood-2005-01-0143. Epub 2005 May 19.

  PMID: 15905191 BACKGROUND

• Pui CH, Pei D, Sandlund JT, Campana D, Ribeiro RC, Razzouk BI, Rubnitz JE, Howard SC, Hijiya N, Jeha S, Cheng C, Downing JR, Evans WE, Relling MV, Hudson M. Risk of adverse events after completion of therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005 Nov 1;23(31):7936-41. doi: 10.1200/JCO.2004.01.0033.

  PMID: 16258093 BACKGROUND

• Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006 Jan 12;354(2):166-78. doi: 10.1056/NEJMra052603. No abstract available.

  PMID: 16407512 BACKGROUND

• Flotho C, Coustan-Smith E, Pei D, Iwamoto S, Song G, Cheng C, Pui CH, Downing JR, Campana D. Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2. Blood. 2006 Aug 1;108(3):1050-7. doi: 10.1182/blood-2006-01-0322. Epub 2006 Apr 20.

  PMID: 16627760 BACKGROUND

• Raimondi SC, Zhou Y, Shurtleff SA, Rubnitz JE, Pui CH, Behm FG. Near-triploidy and near-tetraploidy in childhood acute lymphoblastic leukemia: association with B-lineage blast cells carrying the ETV6-RUNX1 fusion, T-lineage immunophenotype, and favorable outcome. Cancer Genet Cytogenet. 2006 Aug;169(1):50-7. doi: 10.1016/j.cancergencyto.2006.04.006.

  PMID: 16875937 BACKGROUND

• Jeha S, Behm F, Pei D, Sandlund JT, Ribeiro RC, Razzouk BI, Rubnitz JE, Hijiya N, Howard SC, Cheng C, Pui CH. Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2006 Nov 15;108(10):3302-4. doi: 10.1182/blood-2006-04-016709. Epub 2006 Aug 8.

  PMID: 16896151 BACKGROUND

• Hijiya N, Panetta JC, Zhou Y, Kyzer EP, Howard SC, Jeha S, Razzouk BI, Ribeiro RC, Rubnitz JE, Hudson MM, Sandlund JT, Pui CH, Relling MV. Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. Blood. 2006 Dec 15;108(13):3997-4002. doi: 10.1182/blood-2006-05-024414. Epub 2006 Aug 17.

  PMID: 16917005 BACKGROUND

• Madden RM, Pui CH, Hughes WT, Flynn PM, Leung W. Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. Cancer. 2007 Apr 15;109(8):1654-8. doi: 10.1002/cncr.22562.

  PMID: 17345613 BACKGROUND

• Relling MV, Yang W, Das S, Cook EH, Rosner GL, Neel M, Howard S, Ribeiro R, Sandlund JT, Pui CH, Kaste SC. Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. J Clin Oncol. 2004 Oct 1;22(19):3930-6. doi: 10.1200/JCO.2004.11.020.

  PMID: 15459215 BACKGROUND

• Reddick WE, Glass JO, Helton KJ, Langston JW, Li CS, Pui CH. A quantitative MR imaging assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation. AJNR Am J Neuroradiol. 2005 Oct;26(9):2371-7.

  PMID: 16219848 BACKGROUND

• Coustan-Smith E, Ribeiro RC, Stow P, Zhou Y, Pui CH, Rivera GK, Pedrosa F, Campana D. A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome. Blood. 2006 Jul 1;108(1):97-102. doi: 10.1182/blood-2006-01-0066. Epub 2006 Mar 14.

  PMID: 16537802 BACKGROUND

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

Prednisone; Dexamethasone; Vincristine; Daunorubicin; pegaspargase; Asparaginase; Methotrexate; Idarubicin; Etoposide; Cyclophosphamide; Cytarabine; Mercaptopurine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Aminopterin; Pterins; Pteridines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines

Study Officials

• Ching-Hon Pui, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 1998
• Primary Completion: July 1, 2002
• Study Completion: July 1, 2002
• Last Updated: March 30, 2011

Record last verified: 2008-06

Locations

US (1)