Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)

This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Ann Arbor Stage II Adult Lymphoblastic Lymphoma; Ann Arbor Stage II Childhood Lymphoblastic Lymphoma; Ann Arbor Stage III Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Childhood Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult Lymphoblastic Lymphoma; Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma
• Intervention / Treatment: Drug: Etoposide; Drug: Ifosfamide; Drug: Daunorubicin Hydrochloride; Drug: Cyclophosphamide; Drug: Vincristine Sulfate; Drug: Doxorubicin Hydrochloride; Drug: Dexamethasone; Drug: Pegaspargase; Drug: Vincristine; Drug: Thioguanine; Radiation: Radiation Therapy; Drug: Doxorubicin; Drug: Daunorubicin; Drug: Cytarabine; Drug: Leucovorin Calcium; Drug: Hydrocortisone Sodium Succinate; Drug: Bortezomib; Drug: Methotrexate; Drug: Mercaptopurine

Detailed Description

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) in patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LLy) who are randomized to a modified augmented Berlin-Frankfurt-Munster (ABFM) backbone versus bortezomib plus the modified ABFM backbone.

SECONDARY OBJECTIVES:

I. To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based induction, additional doses of pegaspargase (PEG-ASP) during induction and delayed intensification (DI), and dexamethasone pulses during maintenance therapy.

II. To determine if prophylactic (presymptomatic) cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified as standard or intermediate risk.

III. To determine the proportion of end of consolidation (EOC) minimal residual disease (MRD) >= 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant (HSCT).

IV. To compare the EFS between very high risk (induction failure) T-LLy patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).

CORRELATIVE OBJECTIVES:

I. To investigate the prognostic significance of day 29 bone marrow (BM) MRD in T-LLy patients.

II. To determine if protein expression patterns can predict bortezomib response and drug resistance in T-ALL.

III. To analyze and target relevant signaling pathways in T-ALL blasts, focusing on early T cell precursor (ETP) acute lymphoblastic leukemia (ALL).

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients are risk assigned based on data from end of induction and/or consolidation therapy; this then modifies the subsequent therapy received.

T-ALL Risk Group Definitions:

Standard Risk (SR): CNS1*, lumbar puncture prior to steroid therapy (not steroid pretreated), Day 29 (end of induction) bone marrow M1, Day 29 bone marrow minimal residual disease (MRD) <=0.01%, no testicular leukemia at diagnosis.

Intermediate Risk (IR): Not SR or VHR.

Very High Risk (VHR): M3 marrow at Day 29 and/or end of consolidation (EOC) MRD >=0.1%.

*CNS2 and CNS3 cannot be SR and are assigned to IR or VHR based on marrow response.

T-LL Risk Group Definitions:

Standard Risk (SR): CNS1*, MRD at diagnosis <1% in bone marrow, lumbar puncture prior to steroid therapy (not steroid pretreated), Day 29 (end of induction) complete response (CR) or partial response (PR).

Intermediate Risk (IR): Not SR or VHR.

Very High Risk (VHR): Stable Disease (SD)/No response (NR) at Day 29 (End of Induction).

*CNS2 and CNS3 cannot be SR and are assigned to IR or VHR based on radiographic response.

ARM A INDUCTION: Patients receive cytarabine intrathecally (IT) at time of diagnostic lumbar puncture (if within 72 hours from start of protocol therapy) OR day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; dexamethasone orally (PO) twice daily (BID) on days 1-28 (no taper); daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 4 and 18; and methotrexate IT on days 8 and 29 (and on days 15 and 22 for central nervous system 3 involvement [CNS3] T-ALL patients).

ARM A CONSOLIDATION: Beginning on day 36 from Induction, patients receive methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 T-ALL or CNS3 T-LLy patients); cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; pegaspargase IV over 1-2 hours on days 15 and 43; and vincristine sulfate IV on days 15, 22, 43, and 50. Patients with persistent testicular disease undergo radiation therapy.

Patients are then assigned to subsequent therapy according to risk assignment. Patients with standard risk (SR) disease receive Interim Maintenance with Capizzi methotrexate (CMTX); patients with intermediate risk (IR) disease receive Interim Maintenance with high-dose methotrexate (HDMTX), Delayed Intensification, and then Interim Maintenance with CMTX; and patients with very high risk (VHR) disease receive 3 HR Intensification Blocks, Delayed Intensification, and then Interim Maintenance with CMTX.

ARM A CMTX INTERIM MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 11, 21, 31, and 41; methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. The next course (based on risk assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM A DELAYED INTENSIFICATION: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days, 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4, 18, and 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. The next course (based on risk assignment) begins on day 64 or when blood counts recover (whichever occurs later).

ARM A HDMTX INTERIM MAINTENANCE: Patients receive high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium IV or PO on days 3-4, 17-18, 31-32, and 45-46; vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. The next course (based on randomization assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK I: Patients receive dexamethasone IV or PO BID on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium IV or PO on days 3-4; vincristine sulfate IV on days 1 and 6; cyclophosphamide IV over 1-6 hours on days 2-4; high-dose cytarabine IV over 3 hours every 12 hours on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. The next course (Intensification Block II) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK II: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium PO or IV on days 3-4; vincristine sulfate IV on days 1 and 6; ifosfamide IV over 1 hour every 12 hours on days 2-4; daunorubicin hydrochloride IV over 30 minutes on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 1 as in Intensification Block I. The next course (Intensification Block III) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK III: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose cytarabine IV over 3 hours every 12 hours on days 1-2; etoposide IV over 1-2 hours every 12 hours on days 3-5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 5 as in Intensification Block I. The next course (based on randomization) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A MAINTENANCE THERAPY: All patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 29 for SR patients during the first 4 cycles); methotrexate IT on day 1 (and day 29 during the first 4 cycles for SR patients and during the first 2 cycles for IR patients). Patients with CNS1-3VHR and CNS2 VHR, and CNS3 IR disease also undergo cranial radiation therapy during the first 4 weeks (cycle 1). Treatment in female patients with T-ALL and patients with T-LLY repeats every 12 weeks for up to 2 years from the start of Interim Maintenance (week 119). Treatment in male patients with T-ALL repeats every 12 weeks for up to 3 years from the start of Interim Maintenance (week 171).

ARM B INDUCTION: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11(1.3 mg/m^2 per dose); and cytarabine, vincristine sulfate, dexamethasone, daunorubicin hydrochloride, pegaspargase, and methotrexate as in Induction Arm A.

ARM B CONSOLIDATION: Beginning on day 36 from Induction, patients receive methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 T-ALL or CNS3 T-LLy patients); cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; pegaspargase IV over 1-2 hours on days 15 and 43; and vincristine sulfate IV on days 15, 22, 43, and 50. Patients with persistent testicular disease undergo radiation therapy.

Patients are then assigned to subsequent therapy according to risk assignment. Patients with standard risk (SR) disease receive Interim Maintenance with Capizzi methotrexate (CMTX); patients with intermediate risk (IR) disease receive Interim Maintenance with high-dose methotrexate (HDMTX), Delayed Intensification, and then Interim Maintenance with CMTX; and patients with very high risk (VHR) disease receive 3 HR Intensification Blocks, Delayed Intensification, and then Interim Maintenance with CMTX.

ARM B CMTX INTERIM MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on days 1, 11, 21, 31, and 41; methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. The next course (based on risk assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM B DELAYED INTENSIFICATION: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18 (1.3 mg/m^2 per dose); and vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate, cyclophosphamide, cytarabine, and thioguanine as in Delayed Intensification Arm A. The next course (based on risk assignment) begins on day 64 or when blood counts recover (whichever occurs later).

ARM B HDMTX INTERIM MAINTENANCE: Patients receive high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium IV or PO on days 3-4, 17-18, 31-32, and 45-46; vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. The next course (based on randomization assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK I: Patients receive dexamethasone IV or PO BID on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium IV or PO on days 3-4; vincristine sulfate IV on days 1 and 6; cyclophosphamide IV over 1-6 hours on days 2-4; high-dose cytarabine IV over 3 hours every 12 hours on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. The next course (Intensification Block II) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK II: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium PO or IV on days 3-4; vincristine sulfate IV on days 1 and 6; ifosfamide IV over 1 hour every 12 hours on days 2-4; daunorubicin hydrochloride IV over 30 minutes on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 1 as in Intensification Block I. The next course (Intensification Block III) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK III: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose cytarabine IV over 3 hours every 12 hours on days 1-2; etoposide IV over 1-2 hours every 12 hours on days 3-5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 5 as in Intensification Block I. The next course (based on randomization) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B MAINTENANCE THERAPY: All patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 29 for SR patients during the first 4 cycles); methotrexate IT on day 1 (and day 29 during the first 4 cycles for SR patients and during the first 2 cycles for IR patients). Patients with CNS1-3VHR and CNS2 VHR, and CNS3 IR disease also undergo cranial radiation therapy during the first 4 weeks (cycle 1). Treatment in female patients with T-ALL and patients with T-LLY repeats every 12 weeks for up to 2 years from the start of Interim Maintenance (week 119). Treatment in male patients with T-ALL repeats every 12 weeks for up to 3 years from the start of Interim Maintenance (week 171).

All treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 10 years.

• Study Type: Interventional
• Enrollment (Actual): 847
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Hunter Regional Mail Centre, New South Wales, Australia, 2310
      • John Hunter Children's Hospital
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital-Adelaide
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Center-Clayton Campus
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • Princess Margaret Hospital for Children
    • Perth, Western Australia, Australia, 6009
      • Perth Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Janeway Child Health Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • The Montreal Children's Hospital of the MUHC
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Auckland
    • Grafton, Auckland, New Zealand, 1145
      • Starship Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
    • Mobile, Alabama, United States, 36604
      • USA Health Strada Patient Care Center
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Banner Children's at Desert
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3591
      • Arkansas Children's Hospital
  • California
    • Downey, California, United States, 90242
      • Kaiser Permanente Downey Medical Center
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Long Beach, California, United States, 90806
      • Miller Children's and Women's Hospital Long Beach
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Madera, California, United States, 93636
      • Valley Children's Hospital
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford University
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Diego, California, United States, 92134
      • Naval Medical Center -San Diego
    • San Francisco, California, United States, 94158
      • UCSF Medical Center-Mission Bay
    • Torrance, California, United States, 90502
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
    • Fort Myers, Florida, United States, 33908
      • Golisano Children's Hospital of Southwest Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic-Jacksonville
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
    • Pensacola, Florida, United States, 32504
      • Nemours Children's Clinic - Pensacola
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Tampa, Florida, United States, 33607
      • Saint Joseph's Hospital/Children's Hospital-Tampa
    • West Palm Beach, Florida, United States, 33407
      • Saint Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital-Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Children's Hospital-Oak Lawn
    • Park Ridge, Illinois, United States, 60068
      • Advocate Children's Hospital-Park Ridge
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
    • Indianapolis, Indiana, United States, 46260
      • Ascension Saint Vincent Indianapolis Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital New Orleans
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Scarborough, Maine, United States, 04074
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02111
      • Tufts Children's Hospital
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • East Lansing, Michigan, United States, 48824
      • Michigan State University Clinical Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital at Spectrum Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Children's Hospital-Royal Oak
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Columbia Regional
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospitals and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital and Medical Center of Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Center
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Paterson, New Jersey, United States, 07503
      • Saint Joseph's Regional Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • New Hyde Park, New York, United States, 11040
      • The Steven and Alexandra Cohen Children's Medical Center of New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Toledo, Ohio, United States, 43608
      • Mercy Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Children's Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Children's Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19134
      • Saint Christopher's Hospital for Children
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital
    • Greenville, South Carolina, United States, 29605
      • BI-LO Charities Children's Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • T C Thompson Children's Hospital
    • Knoxville, Tennessee, United States, 37916
      • East Tennessee Childrens Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • The Children's Hospital at TriStar Centennial
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • El Paso, Texas, United States, 79905
      • El Paso Children's Hospital
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Lubbock, Texas, United States, 79410
      • Covenant Children's Hospital
    • Lubbock, Texas, United States, 79415
      • UMC Cancer Center / UMC Health System
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78207
      • Children's Hospital of San Antonio
    • San Antonio, Texas, United States, 78229
      • Methodist Children's Hospital of South Texas
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center - Portsmouth
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Carilion Children's
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center and Children's Hospital
    • Tacoma, Washington, United States, 98405
      • Mary Bridge Children's Hospital and Health Center
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project:EveryChild (APEC14B1, if open for the classification of ALL patients) prior to treatment and enrollment on AALL1231
• All patients must be > 1 and < 31 years of age

• Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV

  • Note: 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, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (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
  • For T-LLy 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-LLy defined by the submitting institution will be accepted
• All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

• Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:

  • Steroid pretreatment: prednisone or methylprednisolone for =< 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for =< 336 hours (14 days) in the 28 days prior to initiating induction chemotherapy; prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility; the dose of prednisone or methylprednisolone does not affect eligibility
  • Intrathecal cytarabine (the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) system chemotherapy must begin with 72 hours of this IT therapy; or
  • Pretreatment with hydroxyurea; or

  • 600 cGy of chest irradiation, if medically necessary

    • Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone use during sedation to prevent or treat airway edema; inhalation steroids and topical steroids are not considered pretreatment
• Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity
• Uncontrolled seizure disorder
• Diagnosis of Down syndrome (Trisomy 21)
• Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• Patient has hypersensitivity to bortezomib, boron, or mannitol
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and within 30 days of any dose of bortezomib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (combination chemotherapy); Patients receive combination chemotherapy without bortezomib. See Detailed Description.	Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; VP 16213; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942; Asta Z-4942; Cyfos; Holoxan; Holoxane; Ifex; IFO; IFO-Cell; Ifolem; Ifomida; Ifomide; Ifosfamidum; Ifoxan; IFX; Iphosphamid; Iphosphamide; Iso-Endoxan; Isoendoxan; Isophosphamide; Mitoxana; MJF 9325; MJF-9325; Naxamide; Seromida; Tronoxal; Z 4942; Z-4942; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: Adriamycin; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Pegaspargase; Given IV; Other Names: L-Asparaginase with Polyethylene Glycol; Oncaspar; Oncaspar-IV; PEG-Asparaginase; PEG-L-Asparaginase; PEG-L-Asparaginase (Enzon - Kyowa Hakko); PEGLA; Polyethylene Glycol L-Asparaginase; Polyethylene Glycol-L-Asparaginase; Drug: Vincristine; Given IV; Other Names: VCR; Leurocristine; Vincrystine; LCR; Drug: Thioguanine; Given PO; Other Names: 6-TG; 2-Amino 6MP; 2-Amino-1,7-dihydro-6H-purine-6-thione; 2-Amino-6-mercaptopurine; 2-Amino-6-purinethiol; 2-Aminopurin-6-thiol; 2-Aminopurine-6(1H)-thione; 2-Aminopurine-6-thiol; 2-Aminopurine-6-thiol Hemihydrate; 2-Mercapto-6-aminopurine; 6-Amino-2-mercaptopurine; 6-Mercapto-2-aminopurine; 6-Mercaptoguanine; 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI); BW 5071; Lanvis; Tabloid; Thioguanine Hemihydrate; Thioguanine Hydrate; Tioguanin; Tioguanine; Wellcome U3B; WR-1141; X 27; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Daunorubicin; Given IV; Other Names: DNR; Rubidomycin; Daunomycin; Daunorrubicina; Leukaemomycin C; Rubomycin C; Drug: Cytarabine; Given IT, IV, or SC; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Drug: Leucovorin Calcium; Given PO or IV; Other Names: Wellcovorin; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calcium Leucovorin; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; Citrovorum Factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Factor, Citrovorum; Flynoken A; Folaren; Folaxin; FOLI-cell; Foliben; Folidan; Folidar; Folinac; Folinate Calcium; Folinic Acid Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Folinic acid; Drug: Hydrocortisone Sodium Succinate; Given IT; Other Names: (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt; A-Hydrocort; Buccalsone; Corlan; Cortisol Sodium Succinate; Cortop; Efcortelan; Emergent-EZ; Flebocortid; Hidroc Clora; Hycorace; Hydro-Adreson; Hydrocort; Hydrocortisone 21-Sodium Succinate; Hydrocortisone Na Succinate; Kinogen; Nordicort; Nositrol; Sinsurrene; Sodium hydrocortisone succinate; Solu-Cortef; Solu-Glyc; Drug: Methotrexate; Given IT, IV, or PO; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Drug: Mercaptopurine; Give PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785
Experimental: Arm B (combination chemotherapy, bortezomib); Patients receive combination chemotherapy with bortezomib (4 doses at 1.3 mg/m^2 during Induction and 4 doses at 1.3 mg/m^2 during Delayed Intensification). See Detailed Description.	Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; VP 16213; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942; Asta Z-4942; Cyfos; Holoxan; Holoxane; Ifex; IFO; IFO-Cell; Ifolem; Ifomida; Ifomide; Ifosfamidum; Ifoxan; IFX; Iphosphamid; Iphosphamide; Iso-Endoxan; Isoendoxan; Isophosphamide; Mitoxana; MJF 9325; MJF-9325; Naxamide; Seromida; Tronoxal; Z 4942; Z-4942; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: Adriamycin; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Pegaspargase; Given IV; Other Names: L-Asparaginase with Polyethylene Glycol; Oncaspar; Oncaspar-IV; PEG-Asparaginase; PEG-L-Asparaginase; PEG-L-Asparaginase (Enzon - Kyowa Hakko); PEGLA; Polyethylene Glycol L-Asparaginase; Polyethylene Glycol-L-Asparaginase; Drug: Vincristine; Given IV; Other Names: VCR; Leurocristine; Vincrystine; LCR; Drug: Thioguanine; Given PO; Other Names: 6-TG; 2-Amino 6MP; 2-Amino-1,7-dihydro-6H-purine-6-thione; 2-Amino-6-mercaptopurine; 2-Amino-6-purinethiol; 2-Aminopurin-6-thiol; 2-Aminopurine-6(1H)-thione; 2-Aminopurine-6-thiol; 2-Aminopurine-6-thiol Hemihydrate; 2-Mercapto-6-aminopurine; 6-Amino-2-mercaptopurine; 6-Mercapto-2-aminopurine; 6-Mercaptoguanine; 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI); BW 5071; Lanvis; Tabloid; Thioguanine Hemihydrate; Thioguanine Hydrate; Tioguanin; Tioguanine; Wellcome U3B; WR-1141; X 27; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Daunorubicin; Given IV; Other Names: DNR; Rubidomycin; Daunomycin; Daunorrubicina; Leukaemomycin C; Rubomycin C; Drug: Cytarabine; Given IT, IV, or SC; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Drug: Leucovorin Calcium; Given PO or IV; Other Names: Wellcovorin; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calcium Leucovorin; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; Citrovorum Factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Factor, Citrovorum; Flynoken A; Folaren; Folaxin; FOLI-cell; Foliben; Folidan; Folidar; Folinac; Folinate Calcium; Folinic Acid Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Folinic acid; Drug: Hydrocortisone Sodium Succinate; Given IT; Other Names: (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt; A-Hydrocort; Buccalsone; Corlan; Cortisol Sodium Succinate; Cortop; Efcortelan; Emergent-EZ; Flebocortid; Hidroc Clora; Hycorace; Hydro-Adreson; Hydrocort; Hydrocortisone 21-Sodium Succinate; Hydrocortisone Na Succinate; Kinogen; Nordicort; Nositrol; Sinsurrene; Sodium hydrocortisone succinate; Solu-Cortef; Solu-Glyc; Drug: Bortezomib; Given IV; Other Names: Velcade; MLN341; PS-341; LDP 341; [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; PS341; Drug: Methotrexate; Given IT, IV, or PO; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Drug: Mercaptopurine; Give PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients	EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase	Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	3 years from start of therapy by patient
EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT)	EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact.	3 years
Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT)	Cumulative incidence of isolated CNS relapse adjusting for competing risks using the method of: Gray R, A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1141:1154, 1988	3 years
EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3	EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact.	3 years
EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond	EFS for very high risk (VHR) T-LLy patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond	3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David T Teachey, Children's Oncology Group

Publications and helpful links

General Publications

• Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. doi: 10.1200/JCO.21.02678. Epub 2022 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2014
• Primary Completion (Actual): March 31, 2020
• Study Completion (Estimated): September 22, 2024

Study Registration Dates

• First Submitted: April 9, 2014
• First Submitted That Met QC Criteria: April 9, 2014
• First Posted (Estimated): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Micronutrients; Antibiotics, Antineoplastic; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Keratolytic Agents; Reproductive Control Agents; Antidotes; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Cyclophosphamide; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Podophyllotoxin; Leucovorin; Calcium; Levoleucovorin; Bortezomib; Doxorubicin; Liposomal doxorubicin; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Folic Acid; Calcium, Dietary; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Thioguanine; Pegaspargase; 2-Aminopurine
• Other Study ID Numbers: NCI-2014-00712 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180886 (U.S. NIH Grant/Contract); U10CA098543 (U.S. NIH Grant/Contract); s14-01925; AALL1231 (Other Identifier: CTEP)