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

This study has been completed.
Sponsor:
Information provided by:
Associazione Italiana Ematologia Oncologia Pediatrica
ClinicalTrials.gov Identifier:
NCT00613457
First received: January 21, 2008
Last updated: February 12, 2008
Last verified: January 2008
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: dexamethasone
Drug: asparaginase
Drug: Asparaginase
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin
Drug: doxorubicin
Drug: Etoposide
Drug: Ifosfamide
Drug: mercaptopurine
Drug: Methotrexate
Drug: prednisone
Drug: thioguanine
Drug: Vincristine
Drug: Vindesine
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: AIEOP LLA 2000 Multicenter Study for the Diagnosis and Treatment of Childhood Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Associazione Italiana Ematologia Oncologia Pediatrica:

Primary Outcome Measures:
  • Efficacy of dexamethasone vs prednisone during the induction phase [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Event-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Safety and efficacy of treatment reduction during reintensification in standard-risk patients [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • EFS after second delayed reintensification in intermediate-risk patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Outcome after extended reintensification therapy in high-risk patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 2039
Study Start Date: September 2000
Study Completion Date: July 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: I
o Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on days 8-28.
Drug: asparaginase
native E-coli Asparaginase 5,000 IU/sqm x 8 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: 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: 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
Experimental: II
o Arm II (closed to accrual as of 6/30/2006): Patients receive dexamethasone (DEXA) on days 8-28.
Drug: dexamethasone
10 mg/sqm/day from for 21 days
Drug: asparaginase
native E-coli Asparaginase 5,000 IU/sqm x 8 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: 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: 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
No Intervention: 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.
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: doxorubicin
30 mg/sqm i.v. x 4 doses in Protocol II and III
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: 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
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.
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: doxorubicin
30 mg/sqm i.v. x 4 doses in Protocol II and III
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: 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
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.
Drug: Asparaginase
native E-Coli Asparaginase 10,000 IU/sqm x 4 doses
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: doxorubicin
30 mg/sqm i.v. x 4 doses in Protocol II and III
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: 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
No Intervention: 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.
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: Methotrexate
by age i.t. in Induction/Protocol M/Protocol II/Protocol III/HR Blocks and maintenance
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
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.
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: Methotrexate
by age i.t. in Induction/Protocol M/Protocol II/Protocol III/HR Blocks and maintenance
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00613457

Sponsors and Collaborators
Associazione Italiana Ematologia Oncologia Pediatrica
Investigators
Study Chair: Giuseppe Masera, MD Clinica Pediatrica Università di milano Bicocca
  More Information

No publications provided by Associazione Italiana Ematologia Oncologia Pediatrica

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

Responsible Party: Giuseppe Masera MD, Clinica Pediatrica Università di MIlano Bicocca
ClinicalTrials.gov Identifier: NCT00613457     History of Changes
Other Study ID Numbers: AIEOP LLA 2000, AIEOP LLA 2000
Study First Received: January 21, 2008
Last Updated: February 12, 2008
Health Authority: ITALY:Agenzia Italiana del Farmaco (AIFA)

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
Liposomal doxorubicin
Etoposide phosphate
Isophosphamide mustard
Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Etoposide
Ifosfamide
Prednisone
Vincristine
Vindesine
BB 1101
Dexamethasone acetate
Dexamethasone 21-phosphate
Antimetabolites

ClinicalTrials.gov processed this record on August 18, 2014