Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00408005

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 T-cell acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: nelarabine Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Intensified Methotrexate, Nelarabine (Compound 506U78; IND #52611) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Radiation Therapy

Drug Information available for: Dexamethasone Cyclophosphamide 6-Mercaptopurine Vincristine Leucovorin Methotrexate Cytarabine hydrochloride Doxorubicin Doxorubicin hydrochloride Citrovorum factor Dexamethasone acetate Doxiproct plus Myocet Nelarabine Pegaspargase Cytarabine Thioguanine Leucovorin Calcium Dexamethasone Sodium Phosphate Vincristine sulfate Folinic acid calcium salt pentahydrate Mercaptopurine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival after initial remission [ Designated as safety issue: No ]
Toxicity of nelarabine [ Designated as safety issue: Yes ]
Safety and efficacy of combination chemotherapy with vs without nelarabine [ Designated as safety issue: Yes ]
Safety and efficacy of high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs escalating-dose methotrexate (without leucovorin calcium rescue) and pegaspargase [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

CNS relapse [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	1380
Study Start Date:	January 2007
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Consolidation arm I (weeks 6-13): Active Comparator Patients receive methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43 and 50; and pegaspargase intramuscularly (IM) on days 15 and 43. Patients with Down syndrome (DS) also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic cranial radiotherapy (CRT) (1,200 cGy/dose) once daily on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: leucovorin calcium Given orally or IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Consolidation arm II (weeks 6-13): Active Comparator Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; MTX IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV or SC on days 8-11, 15-18, 50-53 and 57-60; oral mercaptopurine on days 8-21 and 50-63; vincristine IV on days 22, 29, 64, and 71; and pegaspargase IM on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33. Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT once daily on days 22-28 and 29-35.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Consolidation arm III (weeks 6-13): Active Comparator Patients receive MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm I. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm I.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Consolidation arm IV (weeks 6-13): Active Comparator Patients receive nelarabine, MTX, cyclophosphamide, cytarabine, mercaptopurine, vincristine, and pegaspargase as in arm II. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm II.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Interim maintenance arm I (weeks 14-21): Active Comparator Patients receive vincristine IV and escalating doses of MTX IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 31. Patients with DS also receive oral leucovorin calcium 48 and 60 hours after each MTX IT dose.	Drug: leucovorin calcium Given orally or IV Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV
Interim maintenance arm II (weeks 17-24): Active Comparator Patients receive vincristine, escalating doses of MTX, pegaspargase, and MTX IT as in arm I.	Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: vincristine sulfate Given IV
Interim maintenance arm III (weeks 14-21): Active Comparator Patients receive high-dose methotrexate (HDMTX) IV over 24 hours and vincristine IV on days 1, 15, 29, and 43; oral mercaptopurine on days 1-56; and MTX IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or orally once every 6 hours for 3 doses.	Drug: leucovorin calcium Given orally or IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: vincristine sulfate Given IV
Interim maintenance arm IV (weeks 17-24): Active Comparator Patients receive HDMTX, vincristine, mercaptopurine, MTX IT, and leucovorin calcium as in arm III.	Drug: leucovorin calcium Given orally or IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: vincristine sulfate Given IV
Delayed intensification arm I (weeks 22-30): Active Comparator Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients ≥ 10 years of age and for patients with DS); doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6, AND day 43; MTX IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or SC on days 29-32 and 36-39; and oral thioguanine on days 29-42. Patients with DS also receive oral leucovorin calcium at 48 and 60 hours after each MTX dose.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: dexamethasone Given orally and IV Drug: doxorubicin hydrochloride Given IV Drug: leucovorin calcium Given orally or IV Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Delayed intensification arm II (weeks 25-33): Active Comparator Patients receive vincristine IV on days 1, 8, 15, and 50; dexamethasone IV or orally twice daily on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients ≥ 10 years of age); doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; pegaspargase IM on day 4, 5, OR 6 AND day 50; MTX IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV or SC on days 36-39 and 43-46; and oral thioguanine on days 36-49.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: dexamethasone Given orally and IV Drug: doxorubicin hydrochloride Given IV Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV
Delayed intensification arm III (weeks 22-30): Active Comparator Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, cyclophosphamide, cytarabine, and thioguanine as in arm I. Patients with intermediate- or high-risk disease (CNS1 or CNS2 disease) undergo prophylactic CRT (1,200 cGy/dose) once daily on days 50-54 and 57-59.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: dexamethasone Given orally and IV Drug: doxorubicin hydrochloride Given IV Drug: methotrexate Given IV Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Delayed intensification arm IV (weeks 25-33): Active Comparator Patients receive vincristine, dexamethasone, doxorubicin hydrochloride, pegaspargase, MTX IT, nelarabine, cyclophosphamide, cytarabine, and thioguanine as in arm II. Patients with intermediate- or high-risk disease (CNS 1 or CNS2 disease) undergo prophylactic CRT on days 50-54 and 57-59.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV or subcutaneously Drug: dexamethasone Given orally and IV Drug: doxorubicin hydrochloride Given IV Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: pegaspargase Given intramuscularly Drug: thioguanine Given orally Drug: vincristine sulfate Given IV Radiation: radiation therapy Some patients undergo testicular and/or prophylactic cranial radiotherapy.
Maintenance arm I (week 31 until the end of therapy): Active Comparator Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).	Drug: dexamethasone Given orally and IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: vincristine sulfate Given IV
Maintenance arm II (weeks 34-69): Active Comparator Patients receive vincristine IV on days 1 and 57; oral dexamethasone on days 1-5 and 57-61; oral mercaptopurine once daily on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; MTX IT on day 1; and nelarabine IV over 60 minutes on days 29-33. Treatment (that includes nelarabine) repeats every 84 days for 3 courses. Patients then receive treatment (without nelarabine) as follows: vincristine IV on days 1 and 57; oral dexamethasone on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral MTX on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and MTX IT on day 1. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).	Drug: dexamethasone Given orally and IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: vincristine sulfate Given IV
Maintenance arm III (week 31 until the end of therapy): Active Comparator Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX IT as in arm I. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys).	Drug: dexamethasone Given orally and IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: vincristine sulfate Given IV
Maintenance arm IV (weeks 34-69): Active Comparator Patients receive vincristine, dexamethasone, mercaptopurine, oral MTX, MTX IT, and nelarabine as in arm II. Patients then receive treatment (without nelarabine) as follows: vincristine, dexamethasone, mercaptopurine, oral MTX, and MTX IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys).	Drug: dexamethasone Given orally and IV Drug: mercaptopurine Given orally Drug: methotrexate Given IV Drug: nelarabine Given IV Drug: vincristine sulfate Given IV

Show Detailed Description

Ages Eligible for Study:	1 Year to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Study Chair:	Stuart S. Winter, MD	University of New Mexico
Investigator:	Kimberly Dunsmore, MD	University of Virginia

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000514500, COG-AALL0434
Study First Received:	December 4, 2006
Last Updated:	August 29, 2009
ClinicalTrials.gov Identifier:	NCT00408005 History of Changes
Health Authority:	Unspecified