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CompletedNCT00002700Updated Jun 12, 2013

Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia

A Phase 3 interventional study of asparaginase and cyclophosphamide in Leukemia and Lymphoma, sponsored by European Organisation for Research and Treatment of Cancer - EORTC. Completed at 44 sites in 10 countries. Open to participants aged 15 Years to 60 Years. Per ClinicalTrials.gov, last updated 2013-06-12.

Sponsored by European Organisation for Research and Treatment of Cancer - EORTC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
392
Allocation
Randomized
Ages
15 Years to 60 Years
Sex
All
01

Study summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. Bone marrow transplantation can replace immune cells that were destroyed by chemotherapy.

PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia.

Read the detailed description

OBJECTIVES:

  • Compare the remission induction, toxicity, and duration of remission in patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma treated with prednisone vs dexamethasone plus cyclophosphamide, daunorubicin, and vincristine as induction.
  • Compare the survival and disease-free survival of patients treated with autologous bone marrow transplantation (BMT) followed by low- or high-intensity maintenance chemotherapy with cranial irradiation after consolidation.
  • Determine the relative and disease-free survival of patients treated with autologous or allogeneic BMT after identical induction, consolidation, and conditioning regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and risk group (high vs standard).

Induction

  • Patients are randomized to 1 of 2 treatment arms.

    • Arm I:Patients receive daunorubicin IV on days 1-3 and 15 and 16; cyclophosphamide (CTX) IV on days 1 and 8; vincristine (VCR) IV on days 1, 8, 15, and 22; and prednisone IV or orally every 8 hours on days 1-7 and 15-21.
    • Arm II: Patients receive daunorubicin, CTX, and VCR as in arm I and dexamethasone IV or orally on days 1-8 and 15-22.
  • Patients on both arms without CNS disease at presentation receive CNS prophylaxis comprising methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22. Patients on both arms with CNS disease at presentation receive CNS therapy comprising hydrocortisone (HC) IT and MTX IT alternating with cytarabine (ARA-C) IT twice a week until CSF clears. After induction, patients on both arms proceed to consolidation, regardless of response.

Consolidation

  • Patients receive ARA-C IV over 2 hours every 12 hours on days 29-34 and mitoxantrone IV on days 33-35. Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on day 29. Patients with CNS disease at presentation receive CNS therapy comprising HC IT and MTX IT alternating with ARA-C weekly for 6 weeks. Patients who achieve complete response (CR) at day 55-60 receive MTX IV on days 64 and 79, leucovorin calcium IV or orally every 6 hours on days 65-67 and 80-82, and asparaginase IV over 1 hour or intramuscularly on days 65 and 80.
  • Standard-risk patients who are under age 20 and achieve CR after day 80 are assigned to arm IV of group A. Patients who achieve CR after day 80 and have a genotypically or phenotypically HLA-matched family donor, a family donor mismatched at only 1 locus (A, B, or DR), or an HLA-matched unrelated donor proceed to group B. Patients who achieve CR after day 80 and are eligible for autologous bone marrow transplantation (BMT) proceed to group A. Patients found to be at extremely high risk are taken off study.

Group A

  • Patients are randomized to 1 of 2 treatment arms.

    • Arm III: Autologous bone marrow is harvested. Patients receive bone marrow ablation comprising CTX IV over 1 hour on days -4 and -3 and total body irradiation on day -1. Autologous bone marrow is reinfused on day 0. Beginning at month 8 (4 months after BMT), patients receive first maintenance comprising VCR IV, doxorubicin IV, and dexamethasone IV (VAD) or VCR IV, doxorubicin IV, and prednisolone IV (VAP) on days 1-4 and 29-32. Patients receive second maintenance comprising oral mercaptopurine daily and oral MTX daily beginning at month 10 and continuing through year 3. Patients without CNS disease at presentation receive CNS prophylaxis comprising MTX IT on days 1 and 29. Patients with CNS disease at presentation receive CNS therapy comprising ARA-C IT, MTX IT, and HC IT beginning at 1 month after BMT and continuing monthly for 1 year and then every 3 months through year 3.
    • Arm IV: Patients receive CTX IV and ARA-C IV continuously on day 1, oral mercaptopurine on days 8-28, and oral MTX on days 8, 15, and 22 during months 4, 7, 11, 13, 17, 21, 25, and 29. Patients receive MTX IV over 30 minutes on day 1, leucovorin calcium IV or orally every 6 hours on days 2-4, asparaginase IV over 1 hour or intramuscularly on day 2, oral mercaptopurine on days 8-28, and oral MTX on days 8, 15, and 22 during months 6, 10, 12, 15, 19, 23, and 27. Patients receive VAD or VAP as in arm III beginning at month 8. Patients without CNS disease at presentation receive CNS prophylaxis comprising whole brain radiotherapy and MTX IT on day 1 of radiotherapy during month 5. Patients with CNS disease at presentation receive CNS therapy as in arm III.

Group B

  • Allogeneic bone marrow is harvested. Patients receive bone marrow ablation as in arm III beginning on day 100. Allogeneic bone marrow is infused over 15-30 minutes on day 0.

    • Patients in groups A and B with CNS disease at presentation undergo radiotherapy to focal infiltration at entry or concurrently with total body irradiation, or whole brain radiotherapy during maintenance (if no prior CNS irradiation). At any time during the study, patients who develop marrow relapse (more than 5% leukemic blasts in bone marrow on 2 occasions), CNS relapse (blasts in CSF, cranial nerve palsy, or CNS mass), or testis or other extramedullary relapse are taken off study.

PROJECTED ACCRUAL: A total of 392 patients will be accrued for this study within approximately 6 years.

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Conditions studied

  • Leukemia
  • Lymphoma

Keywords

  • untreated adult acute lymphoblastic leukemia
  • stage I adult lymphoblastic lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's planned enrollment of 392 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

European Organisation for Research and Treatment of Cancer - EORTC is the lead sponsor of 342 studies on the registry; 23 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
15 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma with more than 30% blasts in bone marrow

PATIENT CHARACTERISTICS:

Age:

  • 15 to 60

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin less than 2 mg/dL (unless elevation due to leukemic involvement of liver)

Renal:

  • Creatinine less than 2 mg/dL (unless elevation due to leukemic involvement of kidneys)

Cardiovascular:

  • No severe cardiac disease

Pulmonary:

  • No severe pulmonary disease

Other:

  • No severe neurologic or metabolic disease
  • HIV negative (if tested)
  • No other prior malignancy except nonmelanomatous skin cancer, stage I cervical carcinoma, or other curatively treated malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • No prior endocrine therapy

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • No prior surgery
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Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Enrollment
392 participants (estimated)

Interventions

  • Drugasparaginase
  • Drugcyclophosphamide
  • Drugcytarabine
  • Drugdaunorubicin hydrochloride
  • Drugdexamethasone
  • Drugdoxorubicin hydrochloride
  • Drugleucovorin calcium
  • Drugmercaptopurine
  • Drugmethotrexate
  • Drugmitoxantrone hydrochloride
  • Drugprednisolone
  • Drugprednisone
  • Drugtherapeutic hydrocortisone
  • Drugvincristine sulfate
  • Procedureallogeneic bone marrow transplantation
  • Procedureautologous bone marrow transplantation
  • Radiationradiation therapy
06

Study locations

44 sites
  • Algemeen Ziekenhuis Middelheim
    Antwerpen, B-2020, Belgium
  • A.Z. St. Jan
    Brugge, 8000, Belgium
  • C.H.U. Saint-Pierre
    Brussels, 1000, Belgium
  • Hopital Universitaire Erasme
    Brussels, 1070, Belgium
  • Universitair Ziekenhuis Antwerpen
    Edegem, B-2650, Belgium
  • CHU Sart-Tilman
    Liege, B-4000, Belgium
  • Centre Hospitalier Peltzer-La Tourelle
    Verviers, B-4800, Belgium
  • Medical School/University of Zagreb
    Zagreb (Agram), 10000, Croatia
  • University Hospital Rebro
    Zagreb, 10000, Croatia
  • University Hospital - Olomouc
    Olomouc, 775 20, Czech Republic
  • Hopital Edouard Herriot
    Lyon, 69437, France
  • Hotel Dieu de Paris
    Paris, 75181, France
  • Hopital Necker
    Paris, 75743, France
  • Centre Medico-Chirurgical Foch
    Suresnes, 92151, France
  • Kreiskrankenhaus Meissen
    Meissen, D-01662, Germany
  • Ospedale Civile Alessandria
    Alessandria, I-15100, Italy
  • Ospedale Civile Avellino
    Avellino, Italy
  • Universita Degli Studi di Bari Policlinico
    Bari, 70124, Italy
  • A. Perrino Hospital
    Brindisi, 72100, Italy
  • Ospedale Ferrarotto
    Catania, 95124, Italy
  • Ospedale Regionale A. Pugliese
    Catanzaro, 88100, Italy
  • Ospedale Santa Croce
    Cuneo, 12100, Italy
  • Policlinico di Careggi
    Firenze (Florence), 50134, Italy
  • Ospedali Riuniti Foggia
    Foggia, 71100, Italy
  • Ospedale S. Antonio Abate
    Gallarate Varese, 21013, Italy
  • Ospedale Gen. Provinciale Santa Maria Goretti
    Latina, 04100, Italy
  • Ospedale Maggiore Lodi
    Lodi, I-20075, Italy
  • Ospedale Di Montefiascone
    Montefiascone, I-01027, Italy
  • Ospedale S. Gennaro ASL NA1
    Naples (Napoli), 80136, Italy
  • Policlinico - Cattedra di Ematologia
    Palermo, 90100, Italy
  • Policlinico Monteluce
    Perugia, 06122, Italy
  • Ospedale San Carlo
    Potenza, 85100, Italy
  • Ospedale Casa Sollievo della Sofferenza
    San Giovanni - Rotondo, 71013, Italy
  • Istituto di Ematologia Universita - University di Sassari
    Sassari, 07100, Italy
  • Ospedal SS Annunziata
    Taranto, 74100, Italy
  • Ospedale Molinette
    Turin (Torino), 10126, Italy
  • Groot Ziekengasthuis 's-Hertogenbosch
    's-Hertogenbosch, 5211 NL, Netherlands
  • Onze Lieve Vrouwe Gasthuis
    Amsterdam, 1091 HA, Netherlands
  • Maxima Medisch Centrum - locatie Eindhoven
    Eindhoven, 5631 BM, Netherlands
  • Leiden University Medical Center
    Leiden, 2300 CA, Netherlands
  • University Medical Center Nijmegen
    Nijmegen, NL-6500 HB, Netherlands
  • Hospital Escolar San Joao
    Porto, 4200, Portugal
  • Institute of Hematology & Transfusiology, University Hospital
    Bratislava, 85107, Slovakia
  • Ibn-i Sina Hospital
    Ankara, 06100, Turkey
07

References and documents

Publications

  • Reman O, Pigneux A, Huguet F, Vey N, Delannoy A, Fegueux N, de Botton S, Stamatoullas A, Tournilhac O, Buzyn A, Charrin C, Boucheix C, Gabert J, Lheritier V, Vernant JP, Fiere D, Dombret H, Thomas X; GET-LALA group. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008 Nov;32(11):1741-50. doi: 10.1016/j.leukres.2008.04.011. Epub 2008 May 27. PubMed 18508120 ↗
  • Tavernier E, Le QH, de Botton S, Dhedin N, Bulabois CE, Reman O, Vey N, Lheritier V, Dombret H, Thomas X. Secondary or concomitant neoplasms among adults diagnosed with acute lymphoblastic leukemia and treated according to the LALA-87 and LALA-94 trials. Cancer. 2007 Dec 15;110(12):2747-55. doi: 10.1002/cncr.23097. PubMed 17963265 ↗
  • Dhedin N, Dombret H, Thomas X, Lheritier V, Boiron JM, Rigal-Huguet F, Vey N, Kuentz M, Reman O, Witz F, Delannoy A, Kovacsovics T, Bradstock K, Charrin C, Boucheix C, Gabert J, Blaise D, Fiere D, Vernant JP. Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials. Leukemia. 2006 Feb;20(2):336-44. doi: 10.1038/sj.leu.2404065. PubMed 16357838 ↗
  • Picard C, Hayette S, Bilhou-Nabera C, Cayuela JM, Delabesse E, Frenoy N, Preudhomme C, Dupont M, Bastard C, Bories D, Vaerman JL, Davi F, Dastugue N, Raynaud S, Lafage M, Deschaseaux F, Fest T, Gaub MP, Lheritier V, Thomas X, Charrin C, Boucheix C, Dombret H, Macintyre E, Fiere D, Gabert J. Prospective multicentric molecular study for poor prognosis fusion transcripts at diagnosis in adult B-lineage ALL patients: the LALA 94 experience. Leukemia. 2006 Dec;20(12):2178-81. doi: 10.1038/sj.leu.2404408. Epub 2006 Oct 12. No abstract available. PubMed 17039237 ↗
  • Charrin C, Thomas X, Ffrench M, Le QH, Andrieux J, Mozziconacci MJ, Lai JL, Bilhou-Nabera C, Michaux L, Bernheim A, Bastard C, Mossafa H, Perot C, Maarek O, Boucheix C, Lheritier V, Delannoy A, Fiere D, Dastugue N. A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL). Blood. 2004 Oct 15;104(8):2444-51. doi: 10.1182/blood-2003-04-1299. Epub 2004 Mar 23. PubMed 15039281 ↗
  • Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003 Mar 1;21(5):774-80. doi: 10.1200/JCO.2003.02.053. Epub 2003 Mar 1. PubMed 12610173 ↗
  • Labar B, Suciu S, Willemze R, Muus P, Marie JP, Fillet G, Berneman Z, Jaksic B, Feremans W, Bron D, Sinnige H, Mistrik M, Vreugdenhil G, De Bock R, Nemet D, Gilotay C, Amadori S, de Witte T; EORTC Leukemia Group. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group. Haematologica. 2010 Sep;95(9):1489-95. doi: 10.3324/haematol.2009.018580. Epub 2010 Apr 7. PubMed 20378563 ↗
  • Le QH, Thomas X, Ecochard R, Iwaz J, Lheritier V, Michallet M, Fiere D. Proportion of long-term event-free survivors and lifetime of adult patients not cured after a standard acute lymphoblastic leukemia therapeutic program: adult acute lymphoblastic leukemia-94 trial. Cancer. 2007 May 15;109(10):2058-67. doi: 10.1002/cncr.22632. PubMed 17407135 ↗
  • Tavernier E, Boiron JM, Huguet F, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lheritier V, Vernant JP, Dombret H, Thomas X; GET-LALA Group; Swiss Group for Clinical Cancer Research SAKK; Australasian Leukaemia and Lymphoma Group. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia. 2007 Sep;21(9):1907-14. doi: 10.1038/sj.leu.2404824. Epub 2007 Jul 5. PubMed 17611565 ↗
  • Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J; GET-LALA Group the Swiss Group for Clinical Cancer Research (SAKK). Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006 Dec;20(12):2155-61. doi: 10.1038/sj.leu.2404420. Epub 2006 Oct 12. PubMed 17039234 ↗
  • Asnafi V, Buzyn A, Thomas X, Huguet F, Vey N, Boiron JM, Reman O, Cayuela JM, Lheritier V, Vernant JP, Fiere D, Macintyre E, Dombret H. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study. Blood. 2005 Apr 15;105(8):3072-8. doi: 10.1182/blood-2004-09-3666. Epub 2005 Jan 6. PubMed 15637138 ↗
  • Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lheritier V, Fiere D. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86. doi: 10.1200/JCO.2004.10.050. Epub 2004 Sep 7. PubMed 15353542 ↗
  • Asnafi V, Buzyn A, Thomas X, et al.: Impact of immunophenotype and genotype on outcome in LALA94 T-ALLs: toward risk adapted stratification of adult T-ALL. [Abstract] Blood 102 (11): A-67, 2003.
  • Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X, Delannoy A, Buzyn A, Bilhou-Nabera C, Cayuela JM, Fenaux P, Bourhis JH, Fegueux N, Charrin C, Boucheix C, Lheritier V, Esperou H, MacIntyre E, Vernant JP, Fiere D; Groupe d'Etude et de Traitement de la Leucemie Aigue Lymphoblastique de l'Adulte (GET-LALA Group). Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial. Blood. 2002 Oct 1;100(7):2357-66. doi: 10.1182/blood-2002-03-0704. PubMed 12239143 ↗
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 12, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00002700
Lead sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Acute Leukemia French Association
Responsible party
Sponsor
First posted
Jan 27, 2003
Start date
Aug 1995
Primary completion
Mar 2004
Last update
Jun 12, 2013

Study contacts

Roel Willemze, MD, PhD
study chair · Leiden University Medical Center
Denis Fiere, MD
study chair · Acute Leukemia French Association
View the source record on ClinicalTrials.gov ↗

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