A Study to Determine the Outcomes of Patients with Localized B Cell Lymphoblastic Lymphoma (B-LLy) When Treated with Standard Risk B-ALL Therapy

Status: Active

Description

This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in body’s immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better then combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.

Eligibility Criteria

Inclusion Criteria

  • All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731 and MUST submit eligibility studies.
  • Age at diagnosis: * Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS). * Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS). * Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
  • B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
  • B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
  • Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate; * OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy; * OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells; * OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome. * Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
  • All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria

  • Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy.
  • With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
  • For patients receiving steroid pretreatment, the following additional exclusion criteria apply: * Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids. * DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
  • B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
  • Patient must not have acute undifferentiated leukemia (AUL).
  • Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment). * Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
  • Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
  • For LLy patients, the following additional exclusion criteria apply: * T-Lymphoblastic Lymphoma. * Morphologically unclassifiable lymphoma. * Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma. * CNS positive disease or testicular involvement. * M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
  • Female 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 their infants.
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

Locations & Contacts

Alabama

Birmingham
Children's Hospital of Alabama
Status: Active
Contact: Site Public Contact
Phone: 205-638-9285
Email: oncologyresearch@peds.uab.edu
Mobile
USA Health Strada Patient Care Center
Status: Active
Contact: Site Public Contact
Phone: 800-388-8721

Alaska

Anchorage
Providence Alaska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 907-212-6871
Email: AKPAMC.OncologyResearchSupport@providence.org

Arizona

Mesa
Cardon Children's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 602-747-9738
Phoenix
Phoenix Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 602-546-0920

Arkansas

Little Rock
Arkansas Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: Active
Contact: Site Public Contact
Phone: 626-564-3455
Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
Loma Linda
Loma Linda University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 909-558-3375
Long Beach
Miller Children's and Women's Hospital Long Beach
Status: Active
Contact: Site Public Contact
Phone: 562-933-5600
Los Angeles
Cedars Sinai Medical Center
Status: Active
Contact: Site Public Contact
Phone: 310-423-8965
Children's Hospital Los Angeles
Status: Active
Contact: Site Public Contact
Phone: 323-361-4110
Mattel Children's Hospital UCLA
Status: Active
Contact: Site Public Contact
Phone: 310-825-6708
Madera
Valley Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 559-353-3000
Email: Research@valleychildrens.org
Oakland
Kaiser Permanente-Oakland
Status: Active
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: Active
Contact: Site Public Contact
Phone: 714-997-3000
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: Active
Contact: Site Public Contact
Phone: 800-694-0012
Email: ccto-office@stanford.edu
Sacramento
Sutter Medical Center Sacramento
Status: Active
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
University of California Davis Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 916-734-3089
San Diego
Rady Children's Hospital - San Diego
Status: Active
Contact: Site Public Contact
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222
Torrance
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Status: Active
Contact: Site Public Contact
Phone: 310-222-3621

Colorado

Aurora
Children's Hospital Colorado
Status: Active
Contact: Site Public Contact
Phone: 303-764-5056
Email: josh.b.gordon@nsmtp.kp.org
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 303-839-6000

Connecticut

Hartford
Connecticut Children's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 860-545-9981
New Haven
Yale University
Status: Active
Contact: Site Public Contact
Phone: 203-785-5702
Email: canceranswers@yale.edu

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 302-651-6884
Email: dperry@nemours.org

District of Columbia

Washington
Children's National Medical Center
Status: Active
Contact: Site Public Contact
Phone: 202-884-2549
MedStar Georgetown University Hospital
Status: Active
Contact: Site Public Contact
Phone: 202-444-2223

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: Active
Contact: Site Public Contact
Phone: 239-343-5333
Email: molly.arnstrom@leehealth.org
Gainesville
University of Florida Health Science Center - Gainesville
Status: Active
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 954-265-1847
Email: OHR@mhs.net
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: Active
Contact: Site Public Contact
Phone: 904-697-3529
Miami
Miami Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 786-596-2000
Orlando
AdventHealth Orlando
Status: Active
Contact: Site Public Contact
Phone: 407-303-2090
Email: FH.Cancer.Research@flhosp.org
Arnold Palmer Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 321-843-2584
Email: melissa.leffin@orlandohealth.com
Nemours Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 407-650-7150
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 727-767-4784
Email: Ashley.Repp@jhmi.edu
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: Active
Contact: Site Public Contact
Phone: 813-356-7168
Email: Katelynn.Colgain@baycare.org
West Palm Beach
Saint Mary's Hospital
Status: Active
Contact: Site Public Contact
Phone: 561-881-2815

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Active
Contact: Site Public Contact
Phone: 404-785-2025
Email: Leann.Schilling@choa.org
Augusta
Augusta University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 706-721-2388
Email: ga_cares@augusta.edu
Macon
Medical Center of Central Georgia
Status: Active
Contact: Site Public Contact
Phone: 478-633-2152
Email: weatherall.andrew@navicenthealth.org
Savannah
Memorial Health University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: Active
Contact: Site Public Contact
Phone: 808-983-6090

Idaho

Boise
Saint Luke's Mountain States Tumor Institute
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
University of Illinois
Status: Active
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: Active
Contact: Site Public Contact
Phone: 847-723-7570
Park Ridge
Advocate Children's Hospital-Park Ridge
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Peoria
Saint Jude Midwest Affiliate
Status: Active
Contact: Site Public Contact
Phone: 888-226-4343
Springfield
Southern Illinois University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: Active
Contact: Site Public Contact
Phone: 317-338-2194
Email: research@stvincent.org

Iowa

Des Moines
Blank Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 515-241-8912
Email: samantha.mallory@unitypoint.org

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379

Louisiana

New Orleans
Children's Hospital New Orleans
Status: Active
Contact: Site Public Contact
Email: CHResearch@lcmchealth.org
Ochsner Medical Center Jefferson
Status: Active
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org

Maine

Bangor
Eastern Maine Medical Center
Status: Active
Contact: Site Public Contact
Phone: 207-973-4274
Scarborough
Maine Children's Cancer Program
Status: Active
Contact: Site Public Contact
Phone: 207-396-7581
Email: sverwys@mmc.org

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu
Sinai Hospital of Baltimore
Status: Active
Contact: Site Public Contact
Phone: 410-601-6120
Email: pridgely@lifebridgehealth.org
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-888-8823
Bethesda
Walter Reed National Military Medical Center
Status: Active
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Floating Hospital for Children at Tufts Medical Center
Status: Active
Contact: Site Public Contact
Phone: 617-636-5535
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-726-5130
Springfield
Baystate Medical Center
Status: Active
Contact: Site Public Contact
Phone: 413-794-3565
Email: tamara.wrenn@baystatehealth.org
Worcester
UMass Memorial Medical Center - University Campus
Status: Active
Contact: Site Public Contact
Phone: 508-856-3216
Email: cancer.research@umassmed.edu

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-865-1125
Detroit
Ascension Saint John Hospital
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
East Lansing
Michigan State University Clinical Center
Status: Active
Contact: Site Public Contact
Phone: 517-975-9547
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
Bronson Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Royal Oak
Beaumont Children's Hospital-Royal Oak
Status: Active
Contact: Site Public Contact
Phone: 248-551-7695

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: Active
Contact: Site Public Contact
Phone: 612-813-5193
Rochester
Mayo Clinic
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015

Mississippi

Jackson
University of Mississippi Medical Center
Status: Active
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Kansas City
Children's Mercy Hospitals and Clinics
Status: Active
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu
Saint Louis
Cardinal Glennon Children's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 314-268-4000
Mercy Hospital Saint Louis
Status: Active
Contact: Site Public Contact
Phone: 314-251-7066
Washington University School of Medicine
Status: Active
Contact: Site Public Contact
Phone: 800-600-3606
Email: info@siteman.wustl.edu

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: Active
Contact: Site Public Contact
Phone: 402-955-3949
University of Nebraska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Summerlin Hospital Medical Center
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Sunrise Hospital and Medical Center
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
University Medical Center of Southern Nevada
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
Email: cancer.research.nurse@dartmouth.edu

New Jersey

Hackensack
Hackensack University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: Active
Contact: Site Public Contact
Phone: 973-971-5900
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: Active
Contact: Site Public Contact
Phone: 732-235-8675
Saint Peter's University Hospital
Status: Active
Contact: Site Public Contact
Phone: 732-745-8600ext6163
Email: kcovert@saintpetersuh.com
Newark
Newark Beth Israel Medical Center
Status: Active
Contact: Site Public Contact
Phone: 973-926-7230
Paterson
Saint Joseph's Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 973-754-2207
Email: HallL@sjhmc.org

New York

Mineola
NYU Winthrop Hospital
Status: Active
Contact: Site Public Contact
Phone: 516-663-3115
New Hyde Park
The Steven and Alexandra Cohen Children's Medical Center of New York
Status: Active
Contact: Site Public Contact
Phone: 718-470-3460
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Active
Contact: Site Public Contact
Phone: 212-263-4434
Email: prmc.coordinator@nyumc.org
Mount Sinai Hospital
Status: Active
Contact: Site Public Contact
Phone: 212-824-7309
Email: CCTO@mssm.edu
NYP / Weill Cornell Medical Center
Status: Active
Contact: Site Public Contact
Phone: 212-746-1848
Rochester
University of Rochester
Status: Active
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-862-2215
Syracuse
State University of New York Upstate Medical University
Status: Active
Contact: Site Public Contact
Phone: 315-464-5476
Valhalla
New York Medical College
Status: Active
Contact: Site Public Contact
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital Inc-Memorial Campus
Status: Active
Contact: Site Public Contact
Phone: 828-213-4150
Email: leslie.verner@msj.org
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Durham
Duke University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 888-275-3853
Greenville
East Carolina University
Status: Active
Contact: Site Public Contact
Phone: 252-744-1015
Email: eubankss@ecu.edu
Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 336-713-6771

North Dakota

Fargo
Sanford Broadway Medical Center
Status: Active
Contact: Site Public Contact
Phone: 701-323-5760
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: Active
Contact: Site Public Contact
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: Active
Contact: Site Public Contact
Phone: 513-636-2799
Email: cancer@cchmc.org
Cleveland
Cleveland Clinic Foundation
Status: Active
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Rainbow Babies and Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 216-844-5437
Dayton
Dayton Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-228-4055
Toledo
The Toledo Hospital / Toledo Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 503-413-2560
Oregon Health and Science University
Status: Active
Contact: Site Public Contact
Phone: 503-494-1080
Email: trials@ohsu.edu

Pennsylvania

Allentown
Lehigh Valley Hospital-Cedar Crest
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Hershey
Penn State Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: Active
Contact: Site Public Contact
Phone: 267-425-5544
Email: CancerTrials@email.chop.edu
Saint Christopher's Hospital for Children
Status: Active
Contact: Site Public Contact
Phone: 215-427-8991
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: Active
Contact: Site Public Contact
Phone: 412-692-8570
Email: jean.tersak@chp.edu

South Carolina

Columbia
Prisma Health Richland Hospital
Status: Active
Contact: Site Public Contact
Phone: 803-434-3533
Greenville
BI-LO Charities Children's Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 864-522-2066
Email: kim.williams3@prismahealth.org

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: Active
Contact: Site Public Contact
Phone: 605-312-3320
Email: OncologyClinicalTrialsSF@SanfordHealth.org

Tennessee

Chattanooga
T C Thompson Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 865-331-1812
Knoxville
East Tennessee Childrens Hospital
Status: Active
Contact: Site Public Contact
Phone: 865-541-8266
Nashville
The Children's Hospital at TriStar Centennial
Status: Active
Contact: Site Public Contact
Phone: 615-342-1919
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: Active
Contact: Site Public Contact
Phone: 512-628-1902
Email: TXAUS-DL-SFCHemonc.research@ascension.org
Corpus Christi
Driscoll Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 361-694-5311
Email: Crystal.DeLosSantos@dchstx.org
Dallas
Medical City Dallas Hospital
Status: Active
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
El Paso
El Paso Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 915-298-5444
Email: lisa.hartman@ttuhsc.edu
Fort Worth
Cook Children's Medical Center
Status: Active
Contact: Site Public Contact
Phone: 682-885-2103
Email: CookChildrensResearch@cookchildrens.org
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 713-798-1354
Email: burton@bcm.edu
Lubbock
Covenant Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
UMC Cancer Center / UMC Health System
Status: Active
Contact: Site Public Contact
Phone: 806-775-8590
San Antonio
Children's Hospital of San Antonio
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Methodist Children's Hospital of South Texas
Status: Active
Contact: Site Public Contact
Phone: 210-575-6240
Email: Vinod.GidvaniDiaz@hcahealthcare.com
University of Texas Health Science Center at San Antonio
Status: Active
Contact: Site Public Contact
Phone: 210-450-3800
Email: phoresearchoffice@uthscsa.edu
Temple
Scott and White Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 254-724-5407

Vermont

Burlington
University of Vermont and State Agricultural College
Status: Active
Contact: Site Public Contact
Phone: 802-656-8990
Email: rpo@uvm.edu

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu
Falls Church
Inova Fairfax Hospital
Status: Active
Contact: Site Public Contact
Phone: 703-208-6650
Email: Stephanie.VanBebber@inova.org
Norfolk
Children's Hospital of The King's Daughters
Status: Active
Contact: Site Public Contact
Phone: 757-066-8724
Email: CCBDCresearch@chkd.org
Portsmouth
Naval Medical Center - Portsmouth
Status: Active
Contact: Site Public Contact
Phone: 757-953-5939
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 804-628-1914
Email: klcampbell@vcu.edu

Washington

Seattle
Seattle Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-228-6618
Email: HopeBeginsHere@providence.org
Tacoma
Mary Bridge Children's Hospital and Health Center
Status: Active
Contact: Site Public Contact
Phone: 253-403-1461
Email: research@multicare.org

West Virginia

Charleston
West Virginia University Charleston Division
Status: Active
Contact: Site Public Contact
Phone: 304-388-9944
Morgantown
West Virginia University Healthcare
Status: Active
Contact: Site Public Contact
Phone: 304-293-7374
Email: cancertrialsinfo@hsc.wvu.edu

Wisconsin

Green Bay
Saint Vincent Hospital Cancer Center Green Bay
Status: Active
Contact: Site Public Contact
Phone: 920-433-8889
Email: Christy.Gilchrist@hshs.org
Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922
Marshfield
Marshfield Medical Center-Marshfield
Status: Active
Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Milwaukee
Children's Hospital of Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 414-955-4727
Email: MACCCTO@mcw.edu

Australia

Clayton
Monash Medical Center-Clayton Campus
Status: Active
Contact: Site Public Contact
Phone: (03) 9928 8111
Perth
Perth Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
South Brisbane
Queensland Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 61 7 3068 1111

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine in a randomized manner if the addition of 2 cycles of blinatumomab to standard therapy improves disease-free survival (DFS) in patients with standard risk (SR) B-ALL and higher risk features (SR-High), and patients with standard-risk average (SR-Avg) B-ALL who are negative for minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI).

II. To confirm that boys in the standard-risk favorable (SR-Fav) subset of B-ALL, with or without Down syndrome (DS), will maintain a 5-year DFS of greater than 93% when treated with a standard chemotherapy regimen with a treatment duration of 2 years from the start of interim maintenance I (IM1).

SECONDARY OBJECTIVES:

I. To describe the DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of IM1, regardless of sex.

II. To describe the DFS for patients with standard-risk favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen.

III. To determine if patients with DS-High achieve a reduction of treatment-related mortality (TRM) after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of delayed intensification [DI]) with 3 cycles of blinatumomab.

IV. To describe the DFS characterized by the replacement of intensive elements of standard chemotherapy with 3 cycles of blinatumomab in patients with DS-High B ALL.

V. To describe the DFS for patients with localized (Murphy stage I and II) B lymphoblastic lymphoma (B-LLy) receiving standard risk B-ALL therapy.

VI. To compare the change in neurocognitive functioning, as measured by the CogState Cognitive Composite, from baseline to end-of-therapy among patients with ALL ages 4- < 10 years at the time of diagnosis between children from poor families (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH).

VII. To describe the impact of blinatumomab on caregiver burden and patient/proxy-reported symptoms among a subset of children enrolled in the HMH and neurocognitive outcome study.

EXPLORATORY OBJECTIVES:

I. To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL.

II. To explore the impact of acute lymphoblastic leukemia (ALL) and its therapy on neurocognitive, functional, and quality of life outcomes in patients with DS and ALL, as measured by caregiver (parent/legal guardian) questionnaires.

III. To define the prevalence of minimal marrow disease (MMD) in B-LLy and to correlate MMD at diagnosis with outcome in patients with B-LLy.

OUTLINE: All patients are assigned to, and complete an INDUCTION treatment regimen. Patients are then assigned to a CONSOLIDATION treatment regimen. Finally, following CONSOLIDATION, patients are either assigned or randomized to 1 of 7 arms.

NON-DS SR B-ALL INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenous (IV) push over 1 minute on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-28, pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 4, and methotrexate IT on days 8 and 29. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 methotrexate is administered. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* After Non-DS SR B-ALL INDUCTION, SR-Fav and SR-Avg patients complete SR CONSOLIDATION, while patients with SR-High complete high-risk (HR) CONSOLIDATION.

DS B-ALL INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive prednisone or prednisolone PO or IV BID on days 1-28. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 IT methotrexate is administered. CNS3 patients also receive methotrexate IT on days 15 and 22, and leucovorin PO or IV every 6 hours for 2 doses on days 16 and 23. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* After DS B-ALL INDUCTION, patients without high risk features and MRD < 0.01 % complete SR CONSOLIDATION. Patients without high risk features and MRD >= 0.01%, OR with high risk features and any MRD complete HR CONSOLIDATION.

NON-DS B-LLy INDUCTION: Patients receive cytarabine IT on day 1 and twice weekly if CNS2, vincristine IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV BID on days 1-28, pegaspargase IV over 1-2 hours or IM on day 4, and methotrexate IT on days 8 and 29. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* After NON-DS B-LLy INDUCTION, all B-LLy patients then complete SR CONSOLIDATION.

DS B-LLY INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive PO or IV prednisone or methylprednisolone on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* After DS B-LLy INDUCTION, patients then complete SR CONSOLIDATION.

SR CONSOLIDATION: Patients receive vincristine IV push over 1 minute on day 1, mercaptopurine PO on days 1-28, and methotrexate IT on days 1, 8, and 15. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, and 16. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

* After SR CONSOLIDATION, patients with MRD undetectable are assigned to ARM A, and patients with MRD detectable/indeterminate/unavailable are randomized to ARM A or B. Patients with SR-Fav and all B-LLy patients are assigned to treatments identical to that in ARM A.

HR CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, vincristine IV push over 1 minute on days 15, 22, 43, and 50, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (on days 1 and 8 only for DS CNS3 patients), , and pegaspargase IV over 1-2 hours or IM on days 15 and 43. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, 16, and 23 (on days 2 and 9 only for DS CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* After HR CONSOLIDATION, patients are randomized to ARM C or D. DS B-ALL patients with MRD < 1% are assigned to an arm including three blocks of blinatumomab.

ARM A:

* INTERIM MAINTENANCE I: Patients receive vincristine IV push 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, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE II: Patients receive vincristine IV push 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, and methotrexate IT on days 1 and 31. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Non-DS patients receive methotrexate IT on day 1, vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS patients receive vincristine IV push over 1 minute on day 1, methotrexate IT on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78, and leucovorin IV or PO on day 2 if DS. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.

ARM B:

* BLINATUMOMAB BLOCK I: Patients receive dexamethasone IV or PO on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin IV or PO every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE I: Patients receive vincristine IV push 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, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* BLINATUMOMAB BLOCK II: Patients receive methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE II: Patients receive vincristine IV push 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, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Non-DS patients receive methotrexate IT on day 1 (omit on final 2 cycles), vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 on final 2 cycles). DS patients receive methotrexate IT on day 1 (omit on final 2 cycles), dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 except for final 2 cycles), for DS patients and leucovorin IV or PO every 6 hours for 2 doses on day 2 (omit on final 2 cycles). Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.

ARM C:

* INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on day 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive methotrexate IT on days 1, 29, and 36, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Patients receive vincristine IV over 1 minute on day 1, prednisone or prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on days 1 and 29 of cycles 1-2 and on day 1 of subsequent cycles, methotrexate PO on days 8, 15, 22, 29 (for cycle 3 and later only), 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

ARM D:

* BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE I: Patients receive vincristine IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on days 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive methotrexate IT on days 1, 29, and 36, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Patients receive methotrexate IT on day 1, vincristine IV over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

DS-HIGH B-ALL:

* BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV continuously on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, mercaptopurine PO on days 1-56, methotrexate IT on days 1 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 2-4, 16-18, 30-32, and 44-46. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

* BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive vincristine IV over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on day 1, leucovorin PO or IV every 6 hours for 2 doses on day 2, and pegaspargase IV over 1-2 hours or IM on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

* BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV BID on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, methotrexate PO on days 8, 15, 22, 29 (omit day 29 for first 3 cycles for patients who do not receive cranial radiotherapy), 36, 43, 50, 57, 64, 71, and 78, and leucovorin PO on days 2 and 30 (day 30 dose is for cycles 1-3 and for patients who do not receive cranial radiotherapy). CNS3 patients receive cranial radiotherapy during first 4 weeks of cycle 1. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

All B-LLy patients:

* INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* DELAYED INTENSIFICATION: Patients receive vincristine IV push over 1 minute on days 1, 8 and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on days 1 and 29, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients additionally receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* INTERIM MAINTENANCE II: Patients receive vincristine IV push 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, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

* MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DC patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks until complete blood count(CBC)/differential/platelet count recovery, then every 3 months for the first 2 years, then every 4-6 months for the 3rd year, and every 6-12 months for the 4th and 5th years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Childrens Oncology Group

Principal Investigator
Sumit Gupta

Trial IDs

Primary ID AALL1731
Secondary IDs NCI-2019-02187
Clinicaltrials.gov ID NCT03914625