Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia - Full Text View

Sponsored by:	Associazione Italiana Ematologia Oncologia Pediatrica
Information provided by:	Associazione Italiana Ematologia Oncologia Pediatrica
ClinicalTrials.gov Identifier:	NCT00613457

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 III

MedlinePlus related topics: Cancer Leukemia, Childhood

Drug Information available for: Dexamethasone Cyclophosphamide 6-Mercaptopurine Prednisone Vincristine Methotrexate Cytarabine hydrochloride Daunorubicin Doxorubicin Daunorubicin hydrochloride Doxorubicin hydrochloride Etoposide Vindesine Dexamethasone acetate Doxiproct plus Myocet Cytarabine Thioguanine Dexamethasone Sodium Phosphate Vincristine sulfate Ifosfamide Mercaptopurine L-Asparaginase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study
Official Title:	AIEOP LLA 2000 Multicenter Study for the Diagnosis and Treatment of Childhood Acute Lymphoblastic Leukemia

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
I: No Intervention 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
II: Experimental 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
Reintensification Arm I: No Intervention 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
Reintensification Arm II: Experimental 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
Reintensification Arm III: Experimental 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
Reintensification Arm IV: No Intervention 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
Reintensification Arm V: Experimental 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

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

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

Study placed in the following topic categories:

Anti-Inflammatory Agents
Antimetabolites
Acute Lymphoblastic Leukemia, Childhood
Dexamethasone
Daunorubicin
Prednisone
Leukemia, Lymphoid
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Vindesine
Antiemetics
Cyclophosphamide
6-Mercaptopurine
Hormones

Etoposide phosphate
Anti-Bacterial Agents
Leukemia
Methotrexate
Alkylating Agents
Lymphoma
Etoposide
Dexamethasone acetate
Cytarabine
Acute Lymphoblastic Leukemia
Asparaginase
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Antineoplastic Agents, Hormonal
Thioguanine

Additional relevant MeSH terms:

Dexamethasone
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
6-Mercaptopurine
Hormones
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Hormonal
Thioguanine
Vincristine
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Doxorubicin
Neoplasms
Antineoplastic Agents, Phytogenic
Antimetabolites
Daunorubicin

ClinicalTrials.gov processed this record on May 07, 2009