Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

T Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Intensified Methotrexate, Nelarabine (Compound 506U78) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-cell Acute Lymphoblastic Leukemia (ALL) or T-cell Lymphoblastic Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00408005
• Other study ID #: NCI-2009-00307
• Secondary ID: NCI-2009-00307CO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 22, 2007
• Est. completion date: March 7, 2025

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 or T-cell lymphoblastic lymphoma. 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 or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.

Description:

PRIMARY OBJECTIVES:

I. To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group [CCG]-1961).

II. To determine the relative safety and efficacy of high dose methotrexate (5 g/m^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance.

III. To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival.

SECONDARY OBJECTIVES:

I. To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation.

OUTLINE: This is a randomized, controlled, factorial-group, multicenter study.

GROUP 0 (INDUCTION THERAPY): All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; duanorubicin IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease).

GROUP I ARM I COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo conformal radiation therapy (CRT). Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy.

GROUP I ARM I COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID 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 on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II.

GROUP I ARM I COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10).

Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.

GROUP I ARM I COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate 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 with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).

GROUP I ARM II COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours 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 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II.

GROUP I ARM II COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID 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 on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate 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 over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.

GROUP I ARM II COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31.

Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution.

GROUP I ARM II COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate 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 with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).

GROUP I ARM III COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.

GROUP I ARM III COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID 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 on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10).

GROUP I ARM III COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive high dose methotrexate (HDMTX) IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.

GROUP I ARM III COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate 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 with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).

GROUP I ARM IV COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35.

GROUP I ARM IV COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID 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 on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate 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 over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.

GROUP I ARM IV COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.

GROUP I ARM IV COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate 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 with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).

After completion of study therapy, patients are followed periodically for at least 10 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1895
• Est. completion date: March 7, 2025
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

Inclusion Criteria:

• T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434

• Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL) stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory

• T-NHL PATIENTS:

• For T-NHL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-NHL defined by the submitting institution will be accepted

• Prior therapy restrictions

• Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and/or IT cytarabine

• IT chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy

• Patients diagnosed as having T-NHL or T-ALL with respiratory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy; they are eligible for AALL0434 and will be stratified, based on the initial complete blood count (CBC); steroid pretreatment may alter the risk group assessment; if the T-ALL patient's clinical status precludes a lumbar puncture within 48 hours of the initiation of steroid therapy, T-ALL patients CANNOT be classified as low risk and will be Intermediate or high risk based on the results of the day 29 marrow as above; patients with T-NHL who receive steroid pre-treatment will be classified as high risk; the dose and duration of previous steroid therapy should be carefully documented

• For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study

• Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine; in addition, patients with pre-existing grade 2 (or greater) peripheral neurotoxicity, as determined prior to Induction treatment by the treating physician or a neurologist, are not eligible to receive nelarabine; these restrictions in eligibility are designed to prevent excessive nelarabine-induced central and peripheral neurotoxicity in at-risk patients; for the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years

Exclusion Criteria:

• Pregnant or lactating females are ineligible

• Patients with Down syndrome are ineligible to enroll onto this study

• For T-NHL patients the following additional exclusion criteria apply:

• B-precursor lymphoblastic lymphoma

• Morphologically unclassifiable lymphoma

• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma

• CNS3-positive or testicular involvement

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T Acute Lymphoblastic Leukemia
• T Lymphoblastic Lymphoma

Intervention

Drug:
• Asparaginase
Given IM or IV
• Cyclophosphamide
Given IV
• Cytarabine
Given IT, IV, or SC
• Daunorubicin Hydrochloride
Given IV
• Dexamethasone
Given IV or PO
• Doxorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Leucovorin Calcium
Given PO
• Mercaptopurine
Given PO
• Methotrexate
Given IT or PO
• Nelarabine
Given IV
• Pegaspargase
Given IM or IV
• Prednisone
Given IV or PO

Radiation:
• Radiation Therapy
Some patients undergo testicular and/or prophylactic cranial RT

Drug:
• Thioguanine
Given PO
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
Australia	Monash Medical Center-Clayton Campus	Clayton	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Children's Hospital-Brisbane	Herston	Queensland
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Queensland Children's Hospital	South Brisbane	Queensland
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Children's Hospital	London	Ontario
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
Switzerland	Swiss Pediatric Oncology Group - Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group - Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Columbia Regional	Columbia	Missouri
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's and Women's Hospital Long Beach	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Valley Children's Hospital	Madera	California
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Miami Cancer Institute	Miami	Florida
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	USA Health Strada Patient Care Center	Mobile	Alabama
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Carilion Children's	Roanoke	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Mercy Children's Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)	Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.	4 years from randomization at the end of induction
Primary	Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)	Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event	4 years from randomization at the end of induction
Primary	Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)	Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free.	4 years from randomization at the end of induction
Primary	Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)	Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.	4 years from randomization at the end of induction
Primary	Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort	Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.	4 years from end of induction
Secondary	Cumulative Incidence of CNS Relapse for T-ALL by Risk Group	Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation.	4 years from randomization at the end of induction

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.