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Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission

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ClinicalTrials.gov Identifier: NCT00002514
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 22, 2012
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Medical Research Council
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Leukemia Biological: sargramostim Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: imatinib mesylate Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1929 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission
Study Start Date : April 1993
Actual Primary Completion Date : December 2006

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Transplant
Allogeneic (if donor) or Autologous (if no donor) bone marrow transplant
 Biological: sargramostim
Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: imatinib mesylate
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: vincristine sulfate
Procedure: allogeneic bone marrow transplantation
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Active Comparator: Conventional Consolidation/Maintenance
Consolidation/Maintenance Therapy
 Drug: asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: etoposide
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Radiation: radiation therapy


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival [ Time Frame: All patients were followed for 2 years ]

Eligibility Criteria
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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
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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): NCT00002514


  Show 94 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Medical Research Council
Investigators
Study Chair: Jacob M. Rowe, MD Rambam Health Care Campus
Principal Investigator: Mark R. Litzow, MD Mayo Clinic
Study Chair: Antony H. Goldstone, FRCP University College London Hospitals
More Information
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Publications of Results:
Paietta E, Li X, Richards S, et al.: Implications for the use of monoclonal antibodies in future adult ALL trials: analysis of antigen expression in 505 B-lineage (B-Lin) ALL patients (pts) on the MRC UKALLXII/ECOG2993 Intergroup trial. [Abstract] Blood 112 (11): A-1907, 2008.
Rowe JM, Buck G, Moorman AV, et al.: Standard consolidation/maintenance chemotherapy is consistently superior to a single autologous transplant for adult patients with acute lymphoblastic leukemia: results of the international ALL trial (MRC UKALL XII/ECOG E2993). [Abstract] Blood 112 (11): A-3314, 2008.
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.
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.

Other Publications:
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.

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

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00002514     History of Changes
Obsolete Identifiers: NCT00222586
Other Study ID Numbers: CDR0000078099
E2993
MRC-LEUK-UKALL-XII
EST-4491
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: November 22, 2012
Last Verified: August 2007

Keywords provided by Eastern Cooperative Oncology Group:
adult acute lymphoblastic leukemia in remission

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Prednisone
Cyclophosphamide
Methotrexate
Etoposide
Cytarabine
 Vincristine
Imatinib Mesylate
Daunorubicin
Asparaginase
6-Mercaptopurine
Thioguanine
Levoleucovorin
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones