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Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission
This study has been completed.
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Medical Research Council
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002514
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission.


Condition Intervention Phase
Leukemia
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: etoposide
Drug: filgrastim
Drug: imatinib mesylate
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: mitoxantrone hydrochloride
Drug: prednisone
Drug: sargramostim
Drug: thioguanine
Drug: vincristine sulfate
Procedure: allogeneic bone marrow transplantation
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: radiation therapy
Phase III

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood
Drug Information available for: Cyclophosphamide Filgrastim Cytarabine Cytarabine hydrochloride Etoposide Mercaptopurine 6-Mercaptopurine L-Asparaginase Daunorubicin hydrochloride Daunorubicin Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Mitoxantrone hydrochloride Mitoxantrone Prednisone Vincristine sulfate Vincristine Imatinib Imatinib mesylate Sargramostim Granulocyte-macrophage colony-stimulating factor Etoposide phosphate Calcium gluconate Thioguanine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission

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

Primary Outcome Measures:
  • Complete remission [ Designated as safety issue: No ]

Estimated Enrollment: 590
Study Start Date: April 1993
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed acute lymphoblastic leukemia (ALL)

    • More than 25% lymphoblasts in bone marrow

      • Patients with myeloid antigen expression AND unequivocal lymphoid immunophenotype are eligible
  • Philadelphia (Ph) chromosome status determined by cytogenetics, fluorescence in situ hybridization (FISH), and/or RNA analysis

    • Patients determined to be Ph chromosome negative by cytogenetics, but positive for BCR-ABL by FISH or polymerase chain reaction are considered Ph chromosome positive
    • Patients with Ph chromosome-positive disease may be up to age 65
  • No myelodysplasia or other antecedent hematologic disorder
  • Patients age 50 and under must be HLA typed during induction therapy of study treatment OR provide a written explanation for not undergoing HLA typing

    • A and B typing required
    • C and DR typing done if feasible
  • Allogeneic stem cell transplantation patients must meet the following criteria:

    • Appropriate HLA histocompatible donor available

      • Ph chromosome-negative patients must have HLA identical sibling
      • Ph chromosome-positive patients must have HLA identical, HLA-matched unrelated, or haploidentical related donor
  • Postinduction therapy:

    • CSF negative for leukemia
    • No occult or overt leukemic meningitis
    • Documented complete remission

PATIENT CHARACTERISTICS:

Age:

  • 15 to 65

Performance status:

  • Induction therapy:

    • Not specified
  • Postinduction therapy:

    • 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Induction therapy:

    • Direct bilirubin ≤ 2.0 mg/dL
  • Postinduction therapy:

    • Direct bilirubin < 2.0 mg/dL
    • SGPT or SGOT < 3 times normal

Renal:

  • Induction therapy:

    • Creatinine < 2 mg/dL
  • Postinduction therapy:

    • Creatinine ≤ 2 mg/dL
    • Creatinine clearance ≥ 60 mL/min

Cardiovascular:

  • Induction and postinduction therapy:

    • No significant cardiac disease requiring digoxin and/or diuretics
    • No major ventricular dysrhythmia requiring medication
    • No ischemic heart disease requiring medication
  • Postinduction therapy:

    • Cardiac ejection fraction ≥ 50% for patients under consideration for transplantation

Pulmonary:

  • Induction therapy:

    • Not specified
  • Postinduction therapy:

    • FEV_1 ≥ 60% of predicted for patients under consideration for transplantation
    • DLCO ≥ 50% of predicted for patients under consideration for transplantation

Other:

  • Induction and postinduction therapy:

    • HIV negative
    • No concurrent organ damage or other medical problem (e.g., psychiatric disorder or drug abuse) that would preclude study therapy
    • Not pregnant
  • Postinduction therapy:

    • No persistent infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent umbilical cord allogeneic transplantation

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Prior corticosteroids for ALL allowed

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • Induction and postinduction therapy:

    • No other prior therapy for ALL
  • Postinduction therapy:

    • No concurrent antibiotics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002514

  Show 94 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Medical Research Council
Investigators
Study Chair: Jacob M. Rowe, MD Rambam Health Care Campus
Investigator: Mark R. Litzow, MD Mayo Clinic
Study Chair: Antony H. Goldstone, FRCP University College London Hospitals
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from a matched sibling allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy in All patients : final results of the international ALL trial (MRC UKALL XII/ ECOG E2993). Blood. 2007 Nov 29; [Epub ahead of print]
Patel B, Richards SM, Rowe JM, Goldstone AH, Fielding AK. High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis. Leukemia. 2008 Feb;22(2):308-12. Epub 2007 Nov 8.
Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, Durrant IJ, Luger SM, Marks DI, Franklin IM, McMillan AK, Tallman MS, Rowe JM, Goldstone AH; Medical Research Council of the United Kingdom Adult ALL Working Party; Eastern Cooperative Oncology Group. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007 Feb 1;109(3):944-50. Epub 2006 Oct 10.
Fielding AK, Richards SM, Lazarus HM, et al.: Does imatinib change the outcome in Philapdelphia chromosome positive acute lymphoblastic leukaemia in adults? Data from the UKALLXII/ECOG2993 study. [Abstract] Blood 110 (11): A-8, 2007.
Juric D, Lacayo NJ, Ramsey MC, Racevskis J, Wiernik PH, Rowe JM, Goldstone AH, O'dwyer PJ, Paietta E, Sikic BI. Differential Gene Expression Patterns and Interaction Networks in BCR-ABL-Positive and -Negative Adult Acute Lymphoblastic Leukemias. J Clin Oncol. 2007 Mar 5; [Epub ahead of print]
Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, Vance GH, Cherry AM, Higgins RR, Fielding AK, Foroni L, Paietta E, Tallman MS, Litzow MR, Wiernik PH, Rowe JM, Goldstone AH, Dewald GW. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII / Eastern Cooperative Oncology Group (ECOG) 2993 Trial. Blood. 2006 Dec 14; [Epub ahead of print]
Juric D, Lacayo NJ, Ramsey MC, et al.: Differential gene expression patterns and interaction networks in BCR/ABL positive and negative adult acute lymphoblastic leukemias. [Abstract] Blood 108 (11): A-1836, 2006.
Lazarus HM, Richards SM, Chopra R, Litzow MR, Burnett AK, Wiernik PH, Franklin IM, Tallman MS, Cook L, Buck G, Durrant IJ, Rowe JM, Goldstone AH. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis. Results from the International ALL Trial MRC UKALL-XII/ECOG E2993. Blood. 2006 Mar 23; [Epub ahead of print]
Rowe JM, Buck G, Fielding A, et al.: In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from an allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy: final results of the international ALL trial (MRC UKALL XII/ECOG E2993). [Abstract] Blood 108 (11): A-2, 2006.
Moorman AV, Harrison CJ, Richards SM, et al.: Karyotype is an independent prognostic factor in adult acute lymphoblastic leukaemia (ALL): analysis of cytogenetic data from 1,235 patients on the Medical Research Council (MRC) UKALLXII /Eastern Cooperative Oncology Group (ECOG) 2993 trial. [Abstract] Blood 106 (11): A-331, 2005.
Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH. Induction therapy for adults with acute lymphoblastic leukemia (ALL): results of over 1,500 patients from the international ALL Trial: MRC UKALL XII / ECOG E2993. Blood. 2005 Aug 16; [Epub ahead of print]
Goldstone AH, Lazarus HJ, Richards SM, et al.: The outcome of 551 1st CR transplants in adult ALL from the UKALL XII/ECOG 2993 study. [Abstract] Blood 104 (11): A-615, 2004.
Lazarus HM, Richards SM, Chopra R, et al.: Adult patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) leukemia at diagnosis may attain durable complete remissions (CR). Results from the International ALL Trial (MRC UKALL-XII/ECOG E2993) . [Abstract] Blood 104 (11): A-4484, 2004.
Goldstone AH, Chopra R, Buck G, et al.: The outcome of 267 Philadelphia positive adults in the international UKALL12/ECOG E 2993 study. Final analysis and the role of allogeneic transplant in those under 50 years. [Abstract] Blood 102 (11 Pt 1): A-268, 2003.
Rowe JM, Buck G, Burnett AK, et al.: Induction therapy for adults with acute lymphoblastic leukemia (ALL): results of nearly 1,400 patients from the international ALL trial (MRC UKALL XII / ECOG E2993). [Abstract] Blood 102 (11 Pt 1): A-785, 2003.
Ferrando AA, Neuberg D, Dodge RK, et al.: Adult T-cell ALL patients whose lymphoblasts express the HOX11 oncogene have an excellent prognosis when treated with chemotherapy and are not candidates for allogeneic bone marrow transplantaton in first remission. [Abstract] Blood 100 (11 pt 1): A-578, 2002.
Paietta E, Kim H, Racevskis J, et al.: Immunophenotypic characteristics, but not age or secondary cytogenetic changes, affect response and survival of BCR/ABL positive adult acute lymphoblastic leukemia (ALL): ECOG/MRC Intergroup trial, E2993. [Abstract] Blood 100 (11 pt 1): A-2990, 2002.
Goldstone AH, Prentice HG, Durrant J, et al.: Allogeneic transplant (related or unrelated donor) Is the preferred treatment for adult Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL). Results from the international ALL trial (MRC UKALLXII/ECOG E2993). [Abstract] Blood 98 (11 Pt 1): A-3556, 2001.
Paietta E, Kim H, Rowe JM, et al.: Prognostic significance of immunophenotyping and cytogenetics in adult acute lymphoblastic leukemia (ALL): interim analysis of ECOG/MRC phase III intergroup trial, E2993. [Abstract] Blood 98 (11 Pt 1): A-3494, 2001.
Rowe JM, Richards SM, Burnett AK, et al.: Favorable results of allogeneic bone marrow transplantation (BMT) for adults with Philadelphia (Ph)-chromosome-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR): results from the international ALL trial (MRC UKALL XII/ECOG E2993). [Abstract] Blood 98 (11 Pt 1): A-2009, 2001.
Goldstone AH, Richards S, Wiernik PH, et al.: Philadelphia chromosome positive patients with adult acute lymphoblastic leukemia (ALL). Early results from the international ALL trial. [Abstract] Blood 94 (suppl 1): 3071a, 1999.
Rowe JM, Richards S, Wiernik PH, et al.: Allogenic bone marrow transplantation (BMT) for adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR): early results from the international ALL trial. [Abstract] Blood 94 (suppl 1): 732a, 1999.
Paietta E, Racevskis J, Neuberg D, Rowe JM, Goldstone AH, Wiernik PH. Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993. Eastern Cooperative Oncology Group/Medical Research Council. Leukemia. 1997 Nov;11(11):1887-90.

Other Publications:
Study ID Numbers: CDR0000078099, ECOG-2993, MRC-LEUK-UKALL-XII, EST-4491
Study First Received: November 1, 1999
Last Updated: January 10, 2009
ClinicalTrials.gov Identifier: NCT00002514  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute lymphoblastic leukemia in remission

Study placed in the following topic categories:
Dexamethasone
Daunorubicin
Prednisone
Leukemia, Lymphoid
Leucovorin
6-Mercaptopurine
Cyclophosphamide
Etoposide phosphate
Acute lymphoblastic leukemia, adult
Leukemia
Methotrexate
Lymphoma
Etoposide
Dexamethasone acetate
Cytarabine
Asparaginase
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Thioguanine
Vincristine
Folic Acid
Imatinib
Lymphatic Diseases
Calcium, Dietary
Mitoxantrone
Lymphoproliferative Disorders

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Reproductive Control Agents
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Hormones
Sensory System Agents
Vitamins
Therapeutic Uses
Abortifacient Agents
Analgesics
Micronutrients
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Vitamin B Complex
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Growth Substances
Mitosis Modulators
Gastrointestinal Agents

ClinicalTrials.gov processed this record on January 14, 2009