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

This study has been completed.
Sponsor:
Collaborators:
Medical Research Council
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00002514
First received: November 1, 1999
Last updated: November 21, 2012
Last verified: August 2007
  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
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: All patients were followed for 2 years ] [ Designated as safety issue: No ]

Enrollment: 1929
Study Start Date: April 1993
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  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
Principal Investigator: Mark R. Litzow, MD Mayo Clinic
Study Chair: Antony H. Goldstone, FRCP University College London Hospitals
  More Information

Additional Information:
Publications:
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.
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.
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.
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.
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.

Additional 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
Study First Received: November 1, 1999
Last Updated: November 21, 2012
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Cyclophosphamide
Imatinib
Asparaginase
Daunorubicin
Dexamethasone
Etoposide
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on April 23, 2014