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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003728
First received: November 1, 1999
Last updated: January 20, 2011
Last verified: June 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival after first randomization [ Designated as safety issue: No ]
  • Disease-free survival after second and third randomization [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Response to prephase as assessed by number of blasts/mm³ in peripheral blood (< 1,000 vs ≥ 1,000) after randomization [ Designated as safety issue: No ]
  • Response as assessed by bone marrow (BM) blasts after first randomization, at evaluation of prephase, and on day 15 of induction [ Designated as safety issue: No ]
  • Toxicity and long-term toxicity as assessed by CTC v2 [ Designated as safety issue: Yes ]

Estimated Enrollment: 1500
Study Start Date: December 1998
Estimated Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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.

PATIENT CHARACTERISTICS:

Age:

  • Under 18

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Not specified

Renal:

  • Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No prior therapy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003728

Locations
Belgium
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, Belgium, 2020
Hopital Universitaire Des Enfants Reine Fabiola
Brussels, Belgium, 1020
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Ghent University
Ghent, Belgium, B-9000
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Centre Hospitalier Regional de la Citadelle
Liege, Belgium, 4000
Clinique de l'Esperance
Montegnee, Belgium, 4420
France
Centre Hospitalier Regional et Universitaire d'Angers
Angers, France, 49033
CHR de Besancon - Hopital Saint-Jacques
Besancon, France, 25030
CHU de Caen
Caen, France, 14033
CHU de Grenoble - Hopital de la Tronche
Grenoble, France, 38043
Hopital Debrousse
Lyon, France, 69322
Hopital Arnaud de Villeneuve
Montpellier, France, 34059
CHR Hotel Dieu
Nantes, France, 44035
Hopital de l'Archet CHU de Nice
Nice, France, F-06202
CHU - Hopital Robert Debre
Paris, France, 75019
Hopital Jean Bernard
Poitiers, France, 86021
Hopital Americain
Reims, France, 51092
Hopital Universitaire Hautepierre
Strasbourg, France, 67098
Hopital des Enfants
Toulouse, France, 31026
Portugal
Instituto Portugues de Oncologia Centro do Porto, SA
Porto, Portugal, 4200
Hospital Escolar San Joao
Porto, Portugal, 4200
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Investigator: Jacques Otten, MD Academisch Ziekenhuis der Vrije Universiteit Brussel
  More Information

Additional Information:
Publications:
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.
De Moerloose B, Suciu S, Bertrand Y, et al.: Improved outcome with pulses of vincristine and steroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and non Hodgkin lymphoma (NHL): final report of the EORTC randomized phase III trial 58951. [Abstract] Blood 112 (11): A-11, 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.
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00003728     History of Changes
Other Study ID Numbers: CDR0000066840, EORTC-58951
Study First Received: November 1, 1999
Last Updated: January 20, 2011
Health Authority: United States: Federal Government

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:
Leukemia
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
BB 1101
Cortisol succinate
Cyclophosphamide
Daunorubicin
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate

ClinicalTrials.gov processed this record on October 21, 2014