COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Combination Chemotherapy Plus Steroid Therapy in Treating Children With Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkin's Lymphoma

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. Identifier: NCT00003728
Recruitment Status : Unknown
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : January 21, 2011
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy plus steroid therapy is more effective for acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy plus steroid therapy in treating children who have acute lymphoblastic leukemia or lymphoblastic non-Hodgkin's lymphoma.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: methylprednisolone Drug: mitoxantrone hydrochloride Drug: prednisolone Drug: therapeutic hydrocortisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: The Value of Dexamethasone Versus Prednisolone During Induction and Maintenance Therapy of Prolonged Versus Conventional Duration of L-Asparaginase Therapy During Consolidation and Late Intensification, and of Corticosteroid + VCR Pulses During Maintenance in Acute Lymphoblastic Leukemia and Lymphoblastic Non-Hodgkin Lymphoma of Childhood
Study Start Date : December 1998
Estimated Primary Completion Date : May 2008

Primary Outcome Measures :
  1. Event-free survival after first randomization
  2. Disease-free survival after second and third randomization

Secondary Outcome Measures :
  1. Overall survival
  2. Response to prephase as assessed by number of blasts/mm³ in peripheral blood (< 1,000 vs ≥ 1,000) after randomization
  3. Response as assessed by bone marrow (BM) blasts after first randomization, at evaluation of prephase, and on day 15 of induction
  4. Toxicity and long-term toxicity as assessed by CTC v2

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:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed acute lymphoblastic leukemia (ALL) of FAB L1 or L2 morphology

    • Positive SIg allowed OR
  • Histologically confirmed precursor B or precursor T lymphoblastic non-Hodgkin's lymphoma (NHL)

    • No diffuse large cell B-cell lymphoma, Burkitt's lymphoma, or high-grade B-cell lymphoma (Burkitt-like)
  • Very low-risk (VLR) patients meeting 1 of the following criteria:

    • ALL of B-cell lineage

      • WBC less than 10,000/mm^3
      • Must meet 1 of the following conditions:

        • DNA index greater than 1.16 and less than 1.50 and chromosome number 51-66 or unknown
        • DNA index not assessed and chromosome number 51-66
        • DNA index greater than 1.16 and less than 1.50 and chromosome number is unknown
      • Good response to prephase therapy
      • Absence of t(9;22) or BCR/ABL, t(4;11)/MLL-AF4, or 11q23/MLL rearrangement
      • No acute undifferentiated leukemia (AUL)
      • No CNS or gonadal involvement
    • Precursor B-lymphoblastic NHL stage I or II OR
  • Average risk (AR) patients:

    • Must meet 1 of the following criteria:

      • ALL with good response to prephase therapy who are neither VLR or very high risk (VHR)
      • VLR ALL with CNS involvement (CSF positive or negative)
      • Precursor B-lymphoblastic NHL stage III or IV without any VHR feature
      • Precursor T-lymphoblastic NHL
    • AR patients substratified in:

      • AR1: B-cell lineage ALL with WBC less than 100,000/mm^3

        • Surreptitious or hemorrhagic CSF becoming negative at D4 of prephase therapy
        • Precursor B-lymphoblastic NHL stage III or IV
        • Precursor T-lymphoblastic NHL stage I or II
      • AR2: B-cell lineage ALL with WBC at least 100,000/mm^3

        • T-cell lineage ALL regardless of the WBC
        • Overt or non-equivocal CNS involvement at D0 or any CSF involvement at D4
        • Gonadal involvement
        • Precursor T-lymphoblastic NHL stage III or IV
    • Newborn Down syndrome patients with AR2 features are assigned to the AR1 group OR
  • VHR patients:

    • Must meet 1 of the following criteria:

      • ALL patients meeting 1 of the following conditions:

        • Poor response to prephase therapy (at least 1,000/mm^3 blasts in peripheral blood after completion of prephase therapy)
        • t(9;22) or BCR/ABL
        • t(4;11)/MLL-AF4 = 11q23/MLL rearrangement
        • Near haploidy (no more than 34 chromosomes or DNA index less than 0.7)
        • Hypodiploid (35-40 chromosomes or DNA index 0.7 to 0.8)
        • AUL
        • For B lineage ALL: failure to achieve complete response (CR) after completion of protocol IA
        • For T lineage ALL: failure to achieve CR or good partial response (GPR) after completion of protocol IA
        • Minimal-residual disease (greater than 1,000 blasts/100,000 mononuclear bone marrow cells) at evaluation of IA (day 35)
      • NHL patients who failed to achieve CR or GPR after completion of protocol IA
    • All VHR patients are eligible for stem cell transplantation except those whose sole VHR criterion is a poor response to prephase therapy and who have none of the following features:

      • T-cell immunophenotype
      • Early B ALL (CD10 negative)
      • WBC at least 100,000/mm^3
    • Newborn Down syndrome patients with VHR features are assigned to AR1 group NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.



  • Under 18

Performance status:

  • Not specified

Life expectancy:

  • Not specified


  • See Disease Characteristics


  • Not specified


  • Not specified


Biologic therapy:

  • See Disease Characteristics


  • Not specified

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified


  • No prior therapy

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 identifier (NCT number): NCT00003728

Show Show 23 study locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Layout table for investigator information
OverallOfficial: Jacques Otten, MD Academisch Ziekenhuis der Vrije Universiteit Brussel
Publications of Results:
Bertrand Y, Suciu S, Benoit Y, et al.: Dexamethasone(DEX)(6mg/sm/d) and prednisolone(PRED)(60mg/sm/d) in induction therapy of childhood ALL are equally effective: results of the 2nd interim analysis of EORTC trial 58951. [Abstract] Blood 112 (11): A-8, 2008.
Sirvent N, Suciu S, Benoit Y, et al.: Prognostic significance of central nervous system (CNS) status of children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: results of European Organization for Research and Treatment of Cancer (EORTC) Children Leukemia Group study 58951. [Abstract] Blood 112 (11): A-303, 2008.
Bertrand Y, Goutagny MP, Poulat AL, et al.: Asparagine depletion, safety and antibody production after E coli asparaginase treatment in children with newly diagnosed acute lymphoblastic leukaemia treated with EORTC 58951 protocol: a single center report. [Abstract] Blood 110 (11): A-4337, 2007.

Other Publications:
Clappier E, Collette S, Grardel N, et al.: Prognostic significance of NOTCH1 and FBXW7 mutations in childhood T-cell acute lymphoblastic leukemia (T-ALL): results from the EORTC Children Leukemia Group. [Abstract] Blood 114 (22): A-909, 2009.
Renneville A, Kaltenbach S, Clappier E, et al.: Wilms' tumor 1 (WT1) gene mutations in pediatric T-acute lymphoblastic leukemia. [Abstract] Blood 114 (22): A-3075, 2009.
Mirebeau D, Acquaviva C, Suciu S, et al.: Is CDKN2A +/- CDKN2B and MTAP inactivation of prognostic significance in B-precursor childhood acute lymphoblastic leukemia? Results of EORTC studies 58881 and 58951. [Abstract] Blood 104 (11): A-1076, 2004.
Cavé H, Suciu S, Preudhomme C, et al.: HOX11L2 expression linked to t(5;14)(q35;q32) is not associated with poor prognosis in childhood T-ALL treated in EORTC trials 58 881 and 58 951. [Abstract] Blood 100(11 pt 1): A-576, 153a, 2002.

Publications automatically indexed to this study by Identifier (NCT Number):

Layout table for additonal information Identifier: NCT00003728    
Other Study ID Numbers: CDR0000066840
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 21, 2011
Last Verified: June 2009
Keywords provided by National Cancer Institute (NCI):
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
acute undifferentiated leukemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Liposomal doxorubicin