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Therapy for Newly Diagnosed Patients With Acute Lymphoblastic 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: NCT00137111
Recruitment Status : Completed
First Posted : August 29, 2005
Results First Posted : April 26, 2011
Last Update Posted : September 11, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:
The primary objective is to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy and to monitor the molecular remission induction rate.

Condition or disease Intervention/treatment Phase
Lymphoblastic Leukemia, Acute Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide Drug: Mercaptopurine, Imatinib Procedure: chemotherapy, intrathecal chemotherapy Procedure: steroid therapy, hematopoietic stem cell transplantation Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 501 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Actual Study Start Date : July 8, 2000
Actual Primary Completion Date : November 2010
Actual Study Completion Date : April 2014


Arm Intervention/treatment
1 Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin
See Detailed Description sections for details on treatment interventions.

Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase
See Detailed Description sections for details on treatment interventions.

Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide
See Detailed Description sections for details on treatment interventions.

Drug: Mercaptopurine, Imatinib
See Detailed Description sections for details on treatment interventions.

Procedure: chemotherapy, intrathecal chemotherapy
See Detailed Description sections for details on treatment interventions.

Procedure: steroid therapy, hematopoietic stem cell transplantation
See Detailed Description sections for details on treatment interventions.

2 Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin
See Detailed Description sections for details on treatment interventions.

Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase
See Detailed Description sections for details on treatment interventions.

Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide
See Detailed Description sections for details on treatment interventions.

Drug: Mercaptopurine, Imatinib
See Detailed Description sections for details on treatment interventions.

Procedure: chemotherapy, intrathecal chemotherapy
See Detailed Description sections for details on treatment interventions.

Procedure: steroid therapy, hematopoietic stem cell transplantation
See Detailed Description sections for details on treatment interventions.




Primary Outcome Measures :
  1. Overall Event-free Survival (EFS) [ Time Frame: Median follow-up time (range) 5.6 (1.3 to 8.9) years ]
    EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate.

  2. Continuous Complete Remission Since Week 56 Therapy. [ Time Frame: Median follow up time (range) 4.5 (1 to 7.8) years ]
    CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate.


Secondary Outcome Measures :
  1. Minimal Residual Disease (MRD) [ Time Frame: End of Induction (Day 46 MRD measurement) ]
    Detection of MRD at end of induction where positive MRD was defined as one or more leukemic cell per 10,000 mononuclear bone-marrow cells (>=0.01%).

  2. Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours). [ Time Frame: 42 hours after start of high dose methotrexate infusion (HDMTX) ]
    Children were randomly assigned to receive initial single-agent treatment with HDMTX (1g/m^2) as either a 24-hour infusion or a 4-hour infusion and the outcome measure was the accumulation of MTXPG in leukemia cells.

  3. Circulating Leukemia Cells in Peripheral Blood Change From Prior to the Methotrexate Infusion to Three Days After Between Two Arms (4 Hours vs. 24 Hours) [ Time Frame: Immediately before the methotrexate infusion and three days after subsequent infusion ]

    White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count

    Measurement: Percentage change of leukemia cells from baseline



Other Outcome Measures:
  1. Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells [ Time Frame: Pre-treatment ]
    Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of CASP1 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.

  2. Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells [ Time Frame: Pre-treatment ]
    Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of NLRP3 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.



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.


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Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of non-B-cell ALL by immunophenotyping, as determined by the reactivity pattern to a panel of monoclonal antibodies with flow cytometry as well as morphology and cytochemical staining.
  • Age range: 1 to 18 years (inclusive).

Exclusion Criteria:

• Previously treated with chemotherapy for one week or longer.


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): NCT00137111


Locations
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United States, Tennessee
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Sponsors and Collaborators
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ching-Hon Pui, M.D. St. Jude Children's Research Hospital
Additional Information:
Publications:
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012 Jan 11;481(7380):157-63. doi: 10.1038/nature10725.
Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 2013 Mar;45(3):242-52. doi: 10.1038/ng.2532. Epub 2013 Jan 20.
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrozek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014 Sep 11;371(11):1005-15. doi: 10.1056/NEJMoa1403088.
Zhang J, McCastlain K, Yoshihara H, Xu B, Chang Y, Churchman ML, Wu G, Li Y, Wei L, Iacobucci I, Liu Y, Qu C, Wen J, Edmonson M, Payne-Turner D, Kaufmann KB, Takayanagi SI, Wienholds E, Waanders E, Ntziachristos P, Bakogianni S, Wang J, Aifantis I, Roberts KG, Ma J, Song G, Easton J, Mulder HL, Chen X, Newman S, Ma X, Rusch M, Gupta P, Boggs K, Vadodaria B, Dalton J, Liu Y, Valentine ML, Ding L, Lu C, Fulton RS, Fulton L, Tabib Y, Ochoa K, Devidas M, Pei D, Cheng C, Yang J, Evans WE, Relling MV, Pui CH, Jeha S, Harvey RC, Chen IL, Willman CL, Marcucci G, Bloomfield CD, Kohlschmidt J, Mrozek K, Paietta E, Tallman MS, Stock W, Foster MC, Racevskis J, Rowe JM, Luger S, Kornblau SM, Shurtleff SA, Raimondi SC, Mardis ER, Wilson RK, Dick JE, Hunger SP, Loh ML, Downing JR, Mullighan CG; St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nat Genet. 2016 Dec;48(12):1481-1489. doi: 10.1038/ng.3691. Epub 2016 Oct 24.
Alexander TB, Gu Z, Iacobucci I, Dickerson K, Choi JK, Xu B, Payne-Turner D, Yoshihara H, Loh ML, Horan J, Buldini B, Basso G, Elitzur S, de Haas V, Zwaan CM, Yeoh A, Reinhardt D, Tomizawa D, Kiyokawa N, Lammens T, De Moerloose B, Catchpoole D, Hori H, Moorman A, Moore AS, Hrusak O, Meshinchi S, Orgel E, Devidas M, Borowitz M, Wood B, Heerema NA, Carrol A, Yang YL, Smith MA, Davidsen TM, Hermida LC, Gesuwan P, Marra MA, Ma Y, Mungall AJ, Moore RA, Jones SJM, Valentine M, Janke LJ, Rubnitz JE, Pui CH, Ding L, Liu Y, Zhang J, Nichols KE, Downing JR, Cao X, Shi L, Pounds S, Newman S, Pei D, Guidry Auvil JM, Gerhard DS, Hunger SP, Inaba H, Mullighan CG. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018 Oct;562(7727):373-379. doi: 10.1038/s41586-018-0436-0. Epub 2018 Sep 12.
Gu Z, Churchman ML, Roberts KG, Moore I, Zhou X, Nakitandwe J, Hagiwara K, Pelletier S, Gingras S, Berns H, Payne-Turner D, Hill A, Iacobucci I, Shi L, Pounds S, Cheng C, Pei D, Qu C, Newman S, Devidas M, Dai Y, Reshmi SC, Gastier-Foster J, Raetz EA, Borowitz MJ, Wood BL, Carroll WL, Zweidler-McKay PA, Rabin KR, Mattano LA, Maloney KW, Rambaldi A, Spinelli O, Radich JP, Minden MD, Rowe JM, Luger S, Litzow MR, Tallman MS, Racevskis J, Zhang Y, Bhatia R, Kohlschmidt J, Mrozek K, Bloomfield CD, Stock W, Kornblau S, Kantarjian HM, Konopleva M, Evans WE, Jeha S, Pui CH, Yang J, Paietta E, Downing JR, Relling MV, Zhang J, Loh ML, Hunger SP, Mullighan CG. PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. Nat Genet. 2019 Feb;51(2):296-307. doi: 10.1038/s41588-018-0315-5. Epub 2019 Jan 14.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00137111    
Other Study ID Numbers: TOTXV
R37CA036401 ( U.S. NIH Grant/Contract )
P30CA021765 ( U.S. NIH Grant/Contract )
F32CA141762 ( U.S. NIH Grant/Contract )
First Posted: August 29, 2005    Key Record Dates
Results First Posted: April 26, 2011
Last Update Posted: September 11, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Leukemia
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Doxorubicin
Methotrexate
Etoposide
Vincristine
Daunorubicin
Asparaginase
Mercaptopurine
Pegaspargase
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists