Skip to content
Triangle logo TriangleGet started
← Study library

NCT00002514 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2023-06-18

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
65 Years
minimum Age
15 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Allogeneic (if donor) or Autologous (if no donor) bone marrow transplant
    intervention Names
    1. Biological: sargramostim
    2. Drug: asparaginase
    3. Drug: cyclophosphamide
    4. Drug: cytarabine
    5. Drug: daunorubicin hydrochloride
    6. Drug: etoposide
    7. Drug: imatinib mesylate
    8. Drug: leucovorin calcium
    9. Drug: mercaptopurine
    10. Drug: methotrexate
    11. Drug: prednisone
    12. Drug: vincristine sulfate
    label
    Transplant
    type
    EXPERIMENTAL
  2. description
    Consolidation/Maintenance Therapy
    intervention Names
    1. Drug: asparaginase
    2. Drug: cyclophosphamide
    3. Drug: cytarabine
    4. Drug: daunorubicin hydrochloride
    5. Drug: dexamethasone
    6. Drug: etoposide
    7. Drug: leucovorin calcium
    8. Drug: mercaptopurine
    9. Drug: methotrexate
    10. Drug: prednisone
    11. Drug: thioguanine
    12. Drug: vincristine sulfate
    label
    Conventional Consolidation/Maintenance
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Transplant
    name
    sargramostim
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    asparaginase
    type
    DRUG
  3. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    cyclophosphamide
    type
    DRUG
  4. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    cytarabine
    type
    DRUG
  5. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    daunorubicin hydrochloride
    type
    DRUG
  6. arm Group Labels
    1. Conventional Consolidation/Maintenance
    name
    dexamethasone
    type
    DRUG
  7. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    etoposide
    type
    DRUG
  8. arm Group Labels
    1. Transplant
    name
    imatinib mesylate
    type
    DRUG
  9. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    leucovorin calcium
    type
    DRUG
  10. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    mercaptopurine
    type
    DRUG
  11. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    methotrexate
    type
    DRUG
  12. arm Group Labels
    1. Conventional Consolidation/Maintenance
    2. Transplant
    name
    prednisone
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
1929
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Overall Survival
    time Frame
    All patients were followed for 2 years
Full study description
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.
detailed Description
OBJECTIVES: * Compare the duration of complete remission (CR) and survival in patients with acute lymphoblastic leukemia in first remission treated with allogeneic or autologous stem cell transplantation (SCT) vs conventional consolidation and maintenance chemotherapy. * Compare the overall treatment outcomes in patients treated with these regimens. * Determine the effect of imatinib mesylate given after induction therapy in Philadelphia (Ph) chromosome-positive patients in CR. * Determine the benefit of allogeneic or autologous SCT after imatinib mesylate in Ph chromosome-positive patients. * Determine the benefit of additional imatinib mesylate administered after allogeneic or autologous SCT in Ph chromosome-positive patients. * Determine the minimal residual disease in Ph chromosome-positive patients before and after treatment with imatinib mesylate. * Determine the clinical resistance to imatinib mesylate caused by BCR-ABL gene amplification or mutation in Ph chromosome-positive patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (50 and under vs over 50), time to achieve complete remission (CR) (4 weeks or less vs more than 4 weeks), and Philadelphia (Ph) chromosome status (positive vs negative). * First induction therapy: Patients receive daunorubicin (DNR) IV over 15-30 minutes and vincristine (VCR) IV over 3-5 minutes on days 1, 8, 15, and 22; oral prednisone (PRED) once daily on days 1-28; and asparaginase (ASP) IV over 30 minutes or intramuscularly on days 17-28. Patients with CNS leukemia at presentation also receive methotrexate (MTX) intrathecally (IT) via an Ommaya reservoir weekly until the CSF is clear. Patients without CNS leukemia at presentation receive MTX IT on day 23 only. * Second induction therapy: Beginning immediately after first induction therapy, patients receive cyclophosphamide (CTX) IV over 30 minutes on days 1, 15, and 29; cytarabine (ARA-C) IV over 30 minutes on days 1-4, 8-11, 15-18, and 22-25; and oral mercaptopurine (MP) once daily on days 1-28. Patients with CNS leukemia at presentation also undergo concurrent craniospinal irradiation. Patients without CNS leukemia at presentation receive MTX IT on days 1, 8, 15, and 22. Patients with Ph chromosome-positive status receive oral imatinib mesylate once daily for at least 28 days (days 1-28). Patients with Ph chromosome-positive status and CR after second induction therapy proceed to group I for autologous or allogeneic stem cell transplantation (SCT). Patients with Ph chromosome-negative status and CR after second induction therapy proceed to group II. * Group I (Ph chromosome-positive patients): * Autologous SCT: Patients receive high-dose consolidation/mobilization chemotherapy comprising ARA-C IV over 3 hours on days 1-3 and mitoxantrone IV immediately after ARA-C administration on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 5 and continuing until blood counts recover. Patients then undergo peripheral blood stem cell collection or bone marrow harvesting. Patients receive preparative therapy comprising total body irradiation twice daily (5-10 hours apart) on days -6 to -4 and high-dose etoposide (VP-16) IV over 4 hours on day -3. Male patients also undergo radiotherapy boost to the testes on day -6. Patients undergo autologous SCT on day 0 and receive sargramostim (GM-CSF) SC once daily beginning 6 hours after the completion of SCT and continuing until blood counts recover. * Allogeneic SCT: Patients receive the preparative regimen as in autologous SCT and then undergo allogeneic SCT on day 0. Patients receive GM-CSF as in autologous SCT. * Post-SCT imatinib mesylate therapy: After recovery from autologous or allogeneic SCT, patients receive oral imatinib mesylate once daily. Imatinib mesylate therapy continues in the absence of disease progression or unacceptable toxicity. * Group II (Ph chromosome-negative patients): * Intensification therapy: Beginning 4 weeks after the completion of the second induction therapy, patients receive high-dose MTX IV over 2 hours on days 1, 8, and 22; leucovorin calcium IV every 6 hours for 4 doses and then orally every 6 hours for 12 doses beginning 22-24 hours after each MTX infusion; and ASP IV over 30 minutes on days 2, 9, and 23. Patients who are ≤ 50 years of age with a histocompatible donor proceed to allogeneic SCT and undergo allogeneic SCT as in group I. Patients who are ≤ 50 years of age without an appropriate donor are randomized to 1 of 2 treatment arms. * Arm I (conventional consolidation/maintenance therapy): * Conventional consolidation therapy: During course 1, patients receive ARA-C IV over 30 minutes and VP-16 IV over 1 hour on days 1-5; VCR IV on days 1, 8, 15, and 22; and oral dexamethasone on days 1-28. During course 2 (which begins 4 weeks after initiation of course 1 or when blood counts recover), patients receive ARA-C and VP-16 as in course 1. During course 3 (which begins 4 weeks after initiation of course 2 or when blood counts recover), patients receive DNR IV on days 1, 8, 15, and 22; CTX IV over 30 minutes on day 29; ARA-C IV over 30 minutes on days 31-34 and 38-41; and oral thioguanine on days 29-42. During course 4 (which begins 8 weeks after initiation of course 3 or when blood counts recover), patients receive treatment as in course 2. * Maintenance therapy: Beginning 4 weeks after initiation of course 4 of consolidation therapy or when blood counts recover, patients receive oral MP daily; MTX orally or IV once weekly; VCR IV once every 12 weeks; and oral PRED for 5 days every 12 weeks. Maintenance therapy continues for 2.5 years after initiation of intensification therapy. * Arm II (autologous SCT): Patients undergo autologous SCT as in group I with the exception of high-dose consolidation/mobilization chemotherapy. Patients are followed every 6 months for 2 years. PROJECTED ACCRUAL: Approximately 40 patients per year will be accrued for group I (Philadelphia \[Ph\] chromosome-positive patients) of this study. Approximately 550 patients will be accrued for group II (Ph chromosome-negative patients) of this study within 5 years.
Source references
references
  1. citation
    Wang H, Chen XQ, Geng QR, Liu PP, Lin GN, Xia ZJ, Lu Y. Induction therapy using the MRC UKALLXII/ECOG E2993 protocol in Chinese adults with acute lymphoblastic leukemia. Int J Hematol. 2011 Aug;94(2):163-168. doi: 10.1007/s12185-011-0891-y. Epub 2011 Jul 6.
    pmid
    21732037
    type
    BACKGROUND
  2. citation
    Goldstone AH. Transplants in Adult ALL--? Allo for everyone. Biol Blood Marrow Transplant. 2009 Jan;15(1 Suppl):7-10. doi: 10.1016/j.bbmt.2008.11.017.
    pmid
    19147069
    type
    BACKGROUND
  3. citation
    Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A, Rowe J, Webb D. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007 Mar;48(3):254-61. doi: 10.1002/pbc.20749.
    pmid
    16421910
    type
    BACKGROUND
  4. citation
    Paietta E, Ferrando AA, Neuberg D, Bennett JM, Racevskis J, Lazarus H, Dewald G, Rowe JM, Wiernik PH, Tallman MS, Look AT. Activating FLT3 mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias. Blood. 2004 Jul 15;104(2):558-60. doi: 10.1182/blood-2004-01-0168. Epub 2004 Mar 25.
    pmid
    15044257
    type
    BACKGROUND
  5. citation
    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.
    type
    BACKGROUND
  6. citation
    Moorman AV, Schwab C, Ensor HM, Russell LJ, Morrison H, Jones L, Masic D, Patel B, Rowe JM, Tallman M, Goldstone AH, Fielding AK, Harrison CJ. IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. J Clin Oncol. 2012 Sep 1;30(25):3100-8. doi: 10.1200/JCO.2011.40.3907. Epub 2012 Jul 30.
    pmid
    22851563
    type
    RESULT
  7. citation
    Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG2993 trial. Br J Haematol. 2012 May;157(4):463-71. doi: 10.1111/j.1365-2141.2012.09095.x. Epub 2012 Mar 13.
    pmid
    22409379
    type
    RESULT
  8. citation
    Patel B, Rai L, Buck G, Richards SM, Mortuza Y, Mitchell W, Gerrard G, Moorman AV, Duke V, Hoffbrand AV, Fielding AK, Goldstone AH, Foroni L. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010 Jan;148(1):80-9. doi: 10.1111/j.1365-2141.2009.07941.x. Epub 2009 Oct 26.
    pmid
    19863538
    type
    RESULT
  9. citation
    Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. doi: 10.1182/blood-2009-01-199380. Epub 2009 Feb 24.
    pmid
    19244158
    type
    RESULT
  10. citation
    Mansour MR, Sulis ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG, Gale RE, Buck G, Richards S, Paietta E, Rowe JM, Tallman MS, Goldstone AH, Ferrando AA, Linch DC. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol. 2009 Sep 10;27(26):4352-6. doi: 10.1200/JCO.2009.22.0996. Epub 2009 Jul 27.
    pmid
    19635999
    type
    RESULT
  11. citation
    Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. doi: 10.1182/blood-2009-08-231217.
    pmid
    19828704
    type
    RESULT
  12. citation
    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, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. doi: 10.1182/blood-2007-10-116582. Epub 2007 Nov 29.
    pmid
    18048644
    type
    RESULT
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-7a5f00b27aaaf27fb7b5
      requested nct id
      NCT00002514
      primary nct id
      NCT00002514
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      e697833d4abd9767a7115cba8c1fed98c52a5419a6e33d78e513248f19638e90
      payload sha256
      0d22facdf303e6daea3d1b06de1e265805cd4419fcb2c60af8338ad45f888522
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-7a5f00b27aaaf27fb7b5
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT00002514
      occurrences
      1. context exact
        veral trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (<a href="/clinicaltrials/NCT00002514">ECOG-2993</a> [NCT00002514]), of aggressive consolidation chemotherapy for ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40
        end
        82900
        exact text
        NCT00002514
        start
        82889
      2. context exact
        ies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (<a href="/clinicaltrials/NCT00002514">ECOG-2993</a> [NCT00002514]), of aggressive consolidation chemotherapy for ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40%.[<a href="#cit/section_6.1
        end
        82928
        exact text
        NCT00002514
        start
        82917
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/aaea50b1739b09793b.html
      source file sha256
      e697833d4abd9767a7115cba8c1fed98c52a5419a6e33d78e513248f19638e90
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:52.892398+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      3a5c5d02f311c019ea1c519cd09c38b3341949b5c01111d75e3b012b6e87d6d8
      source title
      Acute Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: March 17, 2025
        datetime
        2025-03-17T12:00:00Z
        display
        March 17, 2025

    Preserved source evidence · Not medical advice