Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia (AIEOP LLA 2000)
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ClinicalTrials.gov Identifier: NCT00613457 |
Recruitment Status :
Completed
First Posted : February 13, 2008
Last Update Posted : January 14, 2015
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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 or disease | Intervention/treatment | Phase |
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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 (Clinical Trial) |
Actual Enrollment : | 2039 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | AIEOP LLA 2000 Multicenter Study for the Diagnosis and Treatment of Childhood Acute Lymphoblastic Leukemia |
Study Start Date : | September 2000 |
Actual Primary Completion Date : | July 2006 |
Actual Study Completion Date : | July 2006 |

Arm | Intervention/treatment |
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Experimental: I
o Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on days 8-28.
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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.
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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 |
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.
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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.
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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.
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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 |
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.
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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.
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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 |
- 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 ]

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Ages Eligible for Study: | 1 Year to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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): NCT00613457
Study Chair: | Giuseppe Masera, MD | Clinica Pediatrica Università di milano Bicocca |
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 |
First Posted: | February 13, 2008 Key Record Dates |
Last Update Posted: | January 14, 2015 |
Last Verified: | January 2015 |
Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Prednisone Cyclophosphamide Doxorubicin Liposomal doxorubicin |
Methotrexate Etoposide Vincristine Ifosfamide Isophosphamide mustard Daunorubicin Asparaginase Mercaptopurine Thioguanine Vindesine Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs |