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Trial record 82 of 170 for:    "Acute Lymphocytic Leukemia" | "Etoposide"

Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia (AIEOP LLA 2000)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00613457
Recruitment Status : Completed
First Posted : February 13, 2008
Last Update Posted : January 14, 2015
Sponsor:
Information provided by:
Associazione Italiana Ematologia Oncologia Pediatrica

Tracking Information
First Submitted Date  ICMJE January 21, 2008
First Posted Date  ICMJE February 13, 2008
Last Update Posted Date January 14, 2015
Study Start Date  ICMJE September 2000
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2008)
  • Efficacy of dexamethasone vs prednisone during the induction phase [ Time Frame: 5 years ]
  • Event-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients [ Time Frame: 5 years ]
  • Safety and efficacy of treatment reduction during reintensification in standard-risk patients [ Time Frame: 5 years ]
  • EFS after second delayed reintensification in intermediate-risk patients [ Time Frame: 5 years ]
  • Outcome after extended reintensification therapy in high-risk patients [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00613457 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia
Official Title  ICMJE AIEOP LLA 2000 Multicenter Study for the Diagnosis and Treatment of Childhood Acute Lymphoblastic Leukemia
Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia.

PURPOSE: Thisphase III trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES:

  • Compare the relative efficacy of induction therapy comprising dexamethasone or prednisone, in terms of a higher rate of event-free survival (EFS) and overall survival and a reduced rate of relapse, in pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia (ALL).
  • Compare the relative safety of a reduced-intensity reintensification regimen comprising dexamethasone, vincristine, cyclophosphamide, and anthracyclines vs a standard treatment regimen in pediatric patients with standard-risk ALL identified by fast clearance of leukemic cells.
  • Compare the efficacy of a second delayed reintensification regimen vs standard reintensification therapy, in terms of improved EFS, in pediatric patients with intermediate-risk ALL.
  • Compare the efficacy of extended reintensification therapy (triple reinduction) vs standard reintensification therapy (intensive pulses and one reintensification) in pediatric patients with high-risk ALL.

OUTLINE: This is a randomized, multicenter study.

  • Prednisone prephase therapy: Patients receive oral prednisone on days 1-7 and one dose of methotrexate (MTX) intrathecally (IT) on day 1.
  • Induction/consolidation therapy, protocol I: Patients are randomized to 1 of 2 treatment arms.

    • Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on days 8-28.
    • Arm II (closed to accrual as of 6/30/2006): Patients receive dexamethasone (DEXA) on days 8-28.

Patients in both arms also receive vincristine (VCR) and daunorubicin hydrochloride (DNR) once weekly in weeks 2-5; asparaginase (ASP) on days 12-33; cyclophosphamide (CPM) on days 36 and 64; cytarabine (ARA-C) in weeks 6-9; mercaptopurine (MP) on days 36-63; and MTX IT on days 1, 15, 29,38 and 52.* NOTE: *Patients with CNS disease also receive MTX IT on days 8 and 22. After completion of induction/consolidation therapy, patients are stratified according to risk group based on disease response (standard-risk [SR] group [negative minimal residual disease (MRD) on day 33 and before protocol M, day 78] vs high-risk [HR] group [MRD ≥ 10^-³ on day 78] vs intermediate-risk [IR] group [all nonSR/nonHR]).* Patients with SR and IR disease proceed to consolidation therapy-protocol M. Patients with HR disease proceed to HR block therapy.

NOTE: *Patients meeting any of the following criteria are placed in the HR group regardless of MRD response: Philadelphia chromosome-positive disease (BCR/ABL or t[9;22]; translocations [t4;11][q11;q23] or MLL/AF4); "prednisone-poor-response" (≥ 1,000 blasts/mm³ in the peripheral blood on day 8 after prednisone prephase therapy); or no response to study induction therapy (M2/3 at day 33).

• Consolidation, protocol M: Patients receive MP on days 1-56 and MTX on days 8, 22, 36, and 50.

After completion of extracompartment therapy, SR and IR patients proceed to reintensification therapy. SR patients are randomized to arms I or II. IR patients are randomized to arms I or III. HR patients who have completed induction/consolidation therapy are randomized to arms IV or V.

  • Reinduction therapy:

    o Arm I (standard reinduction therapy, protocol II [closed to accrual as of 6/30/2006]): SR and IR patients receive DEXA on days 1-22; VCR and doxorubicin hydrochloride (DOX) in weeks 2-5; ASP on days 8, 11, 15, and 18; CPM on day 36; ARA-C and thioguanine (TG) on days 36-49; and MTX IT on days 38 and 45. Patients then proceed to maintenance therapy.

  • Arm II (reduced-intensity reinduction therapy, protocol III [closed to accrual as of 6/30/2006]): SR patients receive DEXA on days 1-15; VCR and DOX on days 1 and 8; ASP on days 1, 4, 8, and 11; CPM on day 15; ARA-C and TG on days 15-28; and MTX IT on days 16 and 23. Patients then proceed to maintenance therapy.
  • Arm III (reduced-intensity reinduction/second delayed reinduction therapy [double reintensification therapy] [closed to accrual as of 6/30/2006]): IR patients receive reduced-intensity reintensification therapy as in arm II. After a 10-week interim maintenance phase, treatment repeats once for a second delayed course of reintensification therapy. Patients then proceed to maintenance therapy.
  • Arm IV (standard reintensification therapy [closed to accrual as of 6/30/2006]): HR patients receive one sequence of the following HR therapy elements, in this order: 1, 2, 3, following standard reinduction therapy protocol II repeated twice after a four weeks Interim Maintenance phase. Patients then proceed to maintenance therapy.

    • Element HR-1: Patients receive DEXA on days 1-5; VCR on days 1 and 6; ARA-C twice on day 5; MTX and CPM every 12 hours on days 2-4 (5 doses); ASP on day 6 ; and MTX/ARA-C/PRED IT on day 1.
    • Element HR-2: Patients receive DEXA on days 1-5; vindesine on days 1 and 6; DNR on day 5; MTX and ifosfamide every 12 hours on days 2-4 (5 doses); ASP on day 6; and MTX/ARA-C/PRED IT on day 1.
    • Element HR-3: Patients receive DEXA on days 1-5; ARA-C every 12 hours on days 1-2 (4 doses); etoposide five times daily on days 3-5; ASP on day 5; and MTX/ARA-C/PRED IT on day 1.
  • Arm V (extended reintensification therapy [triple protocol III] [closed to accrual as of 6/30/2006]): HR patients receive HR therapy elements 3, 2, and 1 following reintensification therapy repeated the therapy element three times with 4-week interim maintenance phases in between. Patients then proceed to maintenance therapy.

    • Interim maintenance/maintenance therapy: Patients receive MTX once weekly and MP daily until week 104 plus IT MTX every eight weeks.
    • Radiotherapy: HR patients or patients with T-cell acute lymphoblastic leukemia or CNS disease undergo CNS radiotherapy.

PROJECTED ACCRUAL: A total of 2,039 patients has been accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: dexamethasone
    10 mg/sqm/day from for 21 days
  • Drug: asparaginase
    native E-coli Asparaginase 5,000 IU/sqm x 8 doses
  • Drug: Asparaginase
    native E-Coli Asparaginase 10,000 IU/sqm x 4 doses
  • Drug: cyclophosphamide
    1,000 mg/sqm i.v. 2 doses in Induction phase 1000 mg/sqm i.v. 1 dose in Protocoll II 500 mg/sqm i.v. 1 dose in protocol III
  • Drug: cytarabine
    75 mg/sqm i.v.or s.c. 4 doses/week for 4 weeks in Induction phase 75 mg/sqm i.v.or s.c. 4 doses/week for 2 weeks in Protocol II and III
  • Drug: daunorubicin
    30 mg/sqm i.v. 4 doses in Induction phase
  • Drug: doxorubicin
    30 mg/sqm i.v. x 4 doses in Protocol II and III
  • Drug: Etoposide
    100 mg/sqm i.v. for 3 doses in HR block 3
  • Drug: Ifosfamide
    800 mg/sqm i.v.q12h x 5 in HR block 2
  • Drug: mercaptopurine
    60 mg/sqm p.o. c 28 days in Induction phase 60 mg/sqm p.o. x 56 days in Protocol M 50 mg/sqm daily in Maintenance phase
  • Drug: Methotrexate
    by age i.t. in Induction/Protocol M/Protocol II/Protocol III/HR Blocks and maintenance
  • Drug: prednisone
    60 mg/sqm daily p.o. for 28 days then tapered in Induction phase
  • Drug: thioguanine
    60 mg/sqm p.o. x 14 days in Protocol II and Protocol III
  • Drug: Vincristine
    1.5 mg/sqm i.v. x 4 doses in Induction phase and Protocol II 1.5 mg/sqm i.v. x 2 doses in Protocol III and HR block 1
  • Drug: Vindesine
    3 mg/sqm i.v. x 2 doses in HR block 2
Study Arms  ICMJE
  • Experimental: I
    o Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on days 8-28.
    Interventions:
    • Drug: asparaginase
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: daunorubicin
    • Drug: mercaptopurine
    • Drug: Methotrexate
    • Drug: prednisone
    • Drug: Vincristine
  • Experimental: II
    o Arm II (closed to accrual as of 6/30/2006): Patients receive dexamethasone (DEXA) on days 8-28.
    Interventions:
    • Drug: dexamethasone
    • Drug: asparaginase
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: daunorubicin
    • Drug: mercaptopurine
    • Drug: Methotrexate
    • Drug: Vincristine
  • Experimental: Reintensification Arm I
    o Arm I (standard reinduction therapy, protocol II [closed to accrual as of 6/30/2006]): SR and IR patients receive DEXA on days 1-22; VCR and doxorubicin hydrochloride (DOX) in weeks 2-5; ASP on days 8, 11, 15, and 18; CPM on day 36; ARA-C and thioguanine (TG) on days 36-49; and MTX IT on days 38 and 45. Patients then proceed to maintenance therapy.
    Interventions:
    • Drug: Asparaginase
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: doxorubicin
    • Drug: mercaptopurine
    • Drug: Methotrexate
    • Drug: thioguanine
    • Drug: Vincristine
  • Experimental: Reintensification Arm II
    • Arm II (reduced-intensity reinduction therapy, protocol III [closed to accrual as of 6/30/2006]): SR patients receive DEXA on days 1-15; VCR and DOX on days 1 and 8; ASP on days 1, 4, 8, and 11; CPM on day 15; ARA-C and TG on days 15-28; and MTX IT on days 16 and 23. Patients then proceed to maintenance therapy.
    Interventions:
    • Drug: Asparaginase
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: doxorubicin
    • Drug: mercaptopurine
    • Drug: Methotrexate
    • Drug: thioguanine
    • Drug: Vincristine
  • Experimental: Reintensification Arm III
    • Arm III (reduced-intensity reinduction/second delayed reinduction therapy [double reintensification therapy] [closed to accrual as of 6/30/2006]): IR patients receive reduced-intensity reintensification therapy as in arm II. After a 10-week interim maintenance phase, treatment repeats once for a second delayed course of reintensification therapy. Patients then proceed to maintenance therapy.
    Interventions:
    • Drug: Asparaginase
    • Drug: cytarabine
    • Drug: doxorubicin
    • Drug: mercaptopurine
    • Drug: Methotrexate
    • Drug: Vincristine
  • Experimental: Reintensification Arm IV

    • Arm IV (standard reintensification therapy [closed to accrual as of 6/30/2006]): HR patients receive one sequence of the following HR therapy elements, in this order: 1, 2, 3, following standard reinduction therapy protocol II repeated twice after a four weeks Interim Maintenance phase. Patients then proceed to maintenance therapy.

    • Element HR-1: Patients receive DEXA on days 1-5; VCR on days 1 and 6; ARA-C twice on day 5; MTX and CPM every 12 hours on days 2-4 (5 doses); ASP on day 6 ; and MTX/ARA-C/PRED IT on day 1.
    • Element HR-2: Patients receive DEXA on days 1-5; vindesine on days 1 and 6; DNR on day 5; MTX and ifosfamide every 12 hours on days 2-4 (5 doses); ASP on day 6; and MTX/ARA-C/PRED IT on day 1.
    • Element HR-3: Patients receive DEXA on days 1-5; ARA-C every 12 hours on days 1-2 (4 doses); etoposide five times daily on days 3-5; ASP on day 5; and MTX/ARA-C/PRED IT on day 1.
    Interventions:
    • Drug: Etoposide
    • Drug: Ifosfamide
    • Drug: Methotrexate
    • Drug: Vincristine
    • Drug: Vindesine
  • Experimental: Reintensification Arm V

    • Arm V (extended reintensification therapy [triple protocol III] [closed to accrual as of 6/30/2006]): HR patients receive HR therapy elements 3, 2, and 1 following reintensification therapy repeated the therapy element three times with 4-week interim maintenance phases in between. Patients then proceed to maintenance therapy.

    • Interim maintenance/maintenance therapy: Patients receive MTX once weekly and MP daily until week 104 plus IT MTX every eight weeks.
    • Radiotherapy: HR patients or patients with T-cell acute lymphoblastic leukemia or CNS disease undergo CNS radiotherapy.
    Interventions:
    • Drug: Etoposide
    • Drug: Ifosfamide
    • Drug: Methotrexate
    • Drug: Vincristine
    • Drug: Vindesine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2008)
2039
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2006
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed acute lymphoblastic leukemia (ALL)
  • No secondary ALL
  • More than 4 weeks since prior chemotherapy
  • More than 4 weeks since prior steroids

Exclusion Criteria:

  • Prior disease that would preclude treatment with chemotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00613457
Other Study ID Numbers  ICMJE AIEOP LLA 2000
AIEOP LLA 2000
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Giuseppe Masera MD, Clinica Pediatrica Università di MIlano Bicocca
Study Sponsor  ICMJE Associazione Italiana Ematologia Oncologia Pediatrica
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Giuseppe Masera, MD Clinica Pediatrica Università di milano Bicocca
PRS Account Associazione Italiana Ematologia Oncologia Pediatrica
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP