Combination Chemotherapy in Treating Young Patients with Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

Status: Temporarily Closed to Accrual

Description

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Eligibility Criteria

Inclusion Criteria

  • Patients must be enrolled on APEC14B1 and consented to Eligibility Screening on the Part A consent form prior to enrollment on AALL1131
  • White Blood Cell Count (WBC) Criteria * Age 1-9.99 years: WBC >= 50 000/uL * Age 10-30.99 years: Any WBC * Age 1-30.99 years: Any WBC with: ** Testicular leukemia ** CNS leukemia (CNS3) ** Steroid pretreatment
  • Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
  • Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: * Age: Maximum Serum Creatinine (mg/dL) * 1 to < 6 months: 0.4 (male) 0.4 (female) * 6 months to < 1 year: 0.5 (male) 0.5 (female) * 1 to < 2 years: 0.6 (male) 0.6 (female) * 2 < 6 years: 0.8 (male) 0.8 (female) * 6 to < 10 years: 1.0 (male) 1.0 (female) * 10 to < 13 years: 1.2 (male) 1.2 (female) * 13 to < 16 years: 1.5 (male) 1.4 (female) * > 16 years: 1.7 (male) 1.4 (female)
  • Direct bilirubin =< 3 x upper limit of normal (ULN) for age, and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 x upper limit of normal (ULN) for age
  • Shortening fraction >= 27% by echocardiogram, or ejection fraction >= 50% by gated radionuclide study * Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Friderica or Bazett formula * No major conduction abnormality (unless a cardiac pacemaker is present)
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
  • Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study * Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131 * Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available) * Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William’s Syndrome, mental retardation) * Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
  • Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction
  • Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction: * Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 bone marrow (BM) MRD < 0.01% * With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 BM MRD >= 0.01% * Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria
  • Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131: * Intrachromosomal amplification of chromosome 21 (iAMP21) * Mixed-lineage leukemia (MLL) rearrangement * Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81) * Induction failure (M3 BM at day 29) * Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD >= 0.01%
  • Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction: * Day 29 MRD >= 0.01% * MLL rearrangement * Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
  • DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met

Exclusion Criteria

  • 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 any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131
  • Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction
  • DS HR B-ALL patients with Induction failure or BCR-ABL1
  • Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
  • Lactating females are not eligible unless they have agreed not to breastfeed their infant
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Locations & Contacts

Alabama

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

Alaska

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

Arizona

Mesa
Cardon Children's Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 602-747-9738
Phoenix
Phoenix Childrens Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 602-546-0920
Tucson
Banner University Medical Center - Tucson
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: aselegue@email.arizona.edu

Arkansas

Little Rock
Arkansas Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 626-564-3455
Duarte
City of Hope Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
Loma Linda
Loma Linda University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 909-558-3375
Long Beach
Miller Children's and Women's Hospital Long Beach
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 562-933-5600
Los Angeles
Cedars Sinai Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 310-423-8965
Children's Hospital Los Angeles
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 323-361-4110
Mattel Children's Hospital UCLA
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 310-825-6708
Madera
Valley Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 559-353-3000
Email: Research@valleychildrens.org
Oakland
Children's Hospital and Research Center at Oakland
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 510-428-3324
Email: cgolden@mail.cho.org
Kaiser Permanente-Oakland
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 714-997-3000
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-694-0012
Email: ccto-office@stanford.edu
Sacramento
Sutter Medical Center Sacramento
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 415-209-2686
Email: bernicl@sutterhealth.org
University of California Davis Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 916-734-3089
San Diego
Naval Medical Center -San Diego
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 619-532-8712
Rady Children's Hospital - San Diego
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-827-3222
Santa Barbara
Santa Barbara Cottage Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 805-682-7300
Torrance
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 310-222-3621

Colorado

Aurora
Children's Hospital Colorado
Status: Temporarily closed to accrual
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: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 303-839-6000

Connecticut

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

Delaware

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

District of Columbia

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

Florida

Fort Lauderdale
Broward Health Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 954-355-5346
Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 239-343-5333
Email: molly.arnstrom@leehealth.org
Gainesville
University of Florida Health Science Center - Gainesville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 954-265-1847
Email: OHR@mhs.net
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 904-697-3529
Loxahatchee
Palms West Radiation Therapy
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Miami
Miami Cancer Institute
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 786-596-2000
Nicklaus Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-624-2778
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
AdventHealth Orlando
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 407-303-2090
Email: FH.Cancer.Research@flhosp.org
Arnold Palmer Hospital for Children
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 321-843-2584
Email: melissa.leffin@orlandohealth.com
Nemours Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 407-650-7150
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 727-767-4784
Email: Ashley.Repp@jhmi.edu
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 813-356-7168
Email: Katelynn.Colgain@baycare.org
Tampa General Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 813-844-7829
Email: syapchanyk@tgh.org
West Palm Beach
Saint Mary's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 561-881-2815

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 404-785-2025
Email: Leann.Schilling@choa.org
Augusta
Augusta University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 706-721-2388
Email: ga_cares@augusta.edu
Savannah
Memorial Health University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 808-983-6090

Idaho

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

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 773-880-4562
University of Chicago Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 773-702-8222
Email: cancerclinicaltrials@bsd.uchicago.edu
University of Illinois
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 847-723-7570
Park Ridge
Advocate Children's Hospital-Park Ridge
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Peoria
Saint Jude Midwest Affiliate
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-226-4343
Springfield
Southern Illinois University School of Medicine
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 217-545-7929

Indiana

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

Iowa

Des Moines
Blank Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 515-241-8912
Email: samantha.mallory@unitypoint.org
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 502-629-5500
Email: CancerResource@nortonhealthcare.org

Louisiana

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

Maine

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

Maryland

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

Massachusetts

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

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-865-1125
Detroit
Ascension Saint John Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Wayne State University / Karmanos Cancer Institute
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
East Lansing
Michigan State University Clinical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 517-975-9547
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
Bronson Methodist Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Royal Oak
Beaumont Children's Hospital-Royal Oak
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 248-551-7695

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 612-813-5193
University of Minnesota / Masonic Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 612-624-2620
Rochester
Mayo Clinic
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 855-776-0015

Mississippi

Jackson
University of Mississippi Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

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

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 402-955-3949
University of Nebraska Medical Center
Status: Temporarily closed to accrual
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: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Summerlin Hospital Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
University Medical Center of Southern Nevada
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org

New Hampshire

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

New Jersey

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

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 505-925-0366
Email: LByatt@nmcca.org

New York

Albany
Albany Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 518-262-5513
Bronx
Montefiore Medical Center - Moses Campus
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Buffalo
Roswell Park Cancer Institute
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
Mineola
NYU Winthrop Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 516-663-3115
New Hyde Park
The Steven and Alexandra Cohen Children's Medical Center of New York
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 718-470-3460
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-263-4434
Email: prmc.coordinator@nyumc.org
Mount Sinai Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-824-7309
Email: CCTO@mssm.edu
NYP / Weill Cornell Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 212-746-1848
Rochester
University of Rochester
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-862-2215
Syracuse
State University of New York Upstate Medical University
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 315-464-5476
Valhalla
New York Medical College
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital Inc-Memorial Campus
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 828-213-4150
Email: leslie.verner@msj.org
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-804-9376
Novant Health Presbyterian Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 704-384-5369
Email: nnechiporchik@novanthealth.org
Durham
Duke University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-275-3853
Greenville
East Carolina University
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 252-744-1015
Email: eubankss@ecu.edu
Winston-Salem
Wake Forest University Health Sciences
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 336-713-6771

North Dakota

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

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 513-636-2799
Email: cancer@cchmc.org
Cleveland
Cleveland Clinic Foundation
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-223-8100
Email: CancerAnswer@ccf.org
Rainbow Babies and Childrens Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 614-072-2657
Email: amy.yekisa@nationwidechildrens.org
Dayton
Dayton Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-228-4055
Toledo
Mercy Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-823-5923
Email: ctsucontact@westat.com
The Toledo Hospital / Toledo Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu
Tulsa
Natalie Warren Bryant Cancer Center at Saint Francis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 918-494-2200

Oregon

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

Pennsylvania

Allentown
Lehigh Valley Hospital-Cedar Crest
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Danville
Geisinger Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
Hershey
Penn State Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 267-425-5544
Email: CancerTrials@email.chop.edu
Saint Christopher's Hospital for Children
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 215-427-8991
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 412-692-8570
Email: jean.tersak@chp.edu

Puerto Rico

San Juan
San Jorge Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 787-727-1000
University Pediatric Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 787-474-0333

Rhode Island

Providence
Rhode Island Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 401-444-1488

South Carolina

Charleston
Medical University of South Carolina
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 843-792-9321
Email: hcc-clinical-trials@musc.edu
Columbia
Prisma Health Richland Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 803-434-3533
Greenville
BI-LO Charities Children's Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 864-455-8898

South Dakota

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

Tennessee

Chattanooga
T C Thompson Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 865-331-1812
Knoxville
East Tennessee Childrens Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
St. Jude Children's Research Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-278-5833
Email: info@stjude.org
Nashville
The Children's Hospital at TriStar Centennial
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 615-342-1919
Vanderbilt University / Ingram Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 512-628-1902
Email: TXAUS-DL-SFCHemonc.research@ascension.org
Corpus Christi
Driscoll Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 361-694-5311
Email: Crystal.DeLosSantos@dchstx.org
Dallas
Medical City Dallas Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
El Paso
El Paso Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 915-298-5444
Email: lisa.hartman@ttuhsc.edu
Fort Worth
Cook Children's Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 682-885-2103
Email: CookChildrensResearch@cookchildrens.org
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 713-798-1354
Email: burton@bcm.edu
M D Anderson Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 877-632-6789
Email: askmdanderson@mdanderson.org
Lubbock
Covenant Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
McAllen
Vannie Cook Children's Clinic
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 832-828-1727
Email: jrhartl1@txch.org
San Antonio
Children's Hospital of San Antonio
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Methodist Children's Hospital of South Texas
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 210-575-6240
Email: Vinod.GidvaniDiaz@hcahealthcare.com
University of Texas Health Science Center at San Antonio
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 210-450-3800
Email: phoresearchoffice@uthscsa.edu
Temple
Scott and White Memorial Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 254-724-5407

Utah

Salt Lake City
Primary Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 801-585-5270

Vermont

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

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu
Falls Church
Inova Fairfax Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 703-208-6650
Email: Stephanie.VanBebber@inova.org
Norfolk
Children's Hospital of The King's Daughters
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 757-066-8724
Email: CCBDCresearch@chkd.org
Portsmouth
Naval Medical Center - Portsmouth
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 757-953-5939
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 804-628-1939
Email: mwellons@vcu.edu
Roanoke
Carilion Clinic Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 540-266-6238
Email: wpmccarty@carilionclinic.org

Washington

Seattle
Seattle Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 800-228-6618
Email: HopeBeginsHere@providence.org
Tacoma
Madigan Army Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 253-968-0129
Email: mamcdci@amedd.army.mil
Mary Bridge Children's Hospital and Health Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 253-403-1461
Email: research@multicare.org

West Virginia

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

Wisconsin

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

Alberta

Calgary
Alberta Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 403-220-6898
Email: research4kids@ucalgary.ca
Edmonton
University of Alberta Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 780-407-6615
Email: val.taylor@albertahealthservices.ca

British Columbia

Vancouver
British Columbia Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 604-875-2345ext6477

Manitoba

Winnipeg
CancerCare Manitoba
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-561-1026
Email: ctu_web@cancercare.mb.ca

Newfoundland and Labrador

Saint John's
Janeway Child Health Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 866-722-1126

Nova Scotia

Halifax
IWK Health Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 902-470-6767

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 905-521-2100
Kingston
Kingston Health Sciences Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 613-549-6666
Email: cc-clinicaltrials@kgh.kari.net
London
Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 519-685-8306
Ottawa
Children's Hospital of Eastern Ontario
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 613-738-3931
Toronto
Hospital for Sick Children
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 416-813-7654ext2027
Email: jason.mcguire@sickkids.ca

Quebec

Montreal
The Montreal Children's Hospital of the MUHC
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 514-412-4445
Email: info@thechildren.com

Saskatchewan

Saskatoon
Saskatoon Cancer Centre
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 306-655-2914

Australia

Clayton
Monash Medical Center-Clayton Campus
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: (03) 9928 8111
Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: (02) 4985 5180
North Adelaide
Women's and Children's Hospital-Adelaide
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: (08) 8161 7327
Email: cywhs.oncsec@health.sa.gov.au
Parkville
Royal Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 61 3 9345 5656
Email: Jordan.Hansford@rch.org.au
Perth
Perth Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
South Brisbane
Queensland Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 61 7 3068 1111

Ireland

Dublin
Our Lady's Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 353 1 4096419

New Zealand

Christchurch
Christchurch Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 03 364 0640
Grafton
Starship Children's Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 0800 728 436

Switzerland

Geneva
Swiss Pediatric Oncology Group - Geneva
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 031 389 91 89

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). (Completed effective March 19, 2018)

II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). (Completed effective February 15, 2017)

SECONDARY OBJECTIVES:

I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL. (Completed effective March 19, 2018)

II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL. (Completed effective February 15, 2017)

III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-interim maintenance intermediate dose methotrexate (IMIDM) and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality.

IV. To describe the outcomes for children and young adults with Philadelphia chromosome (Ph)-like B-ALL and a predicted TKI-sensitive mutation treated with dasatinib plus MBFM-IMHDM.

V. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL.

VI. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients.

VII. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON. (Completed accrual July 2016)

VIII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to < 13 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention.

EXPLORATORY OBJECTIVES:

I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm. (Closed effective October 20, 2017)

OUTLINE:

INDUCTION THERAPY:

Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1 (and twice weekly thereafter for CNS2 patients [except for days 8 and 29]); vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 for CNS1 and CNS2 patients (plus days 15 and 22 for CNS3 patients). Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

Participants are stratified to 1 of 3 disease groups: HR B-ALL, VHR B-ALL and PH-like B-ALL a predicted TKI-sensitive mutation.

GROUP I - HR B-ALL: Patients are randomized to 1 of 2 treatment arms. (RANDOMIZATION CLOSED 03/19/2018)

CONSOLIDATION THERAPY (C):

ARM A HR B-ALL C: Patients receive consolidation therapy comprising 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, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL C: Patients receive consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C. (CLOSED 03/19/2018)

INTERIM MAINTENANCE THERAPY (IM)

ARM A HR B-ALL IM: Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018)

DELAYED INTENSIFICATION THERAPY (DI):

ARM A HR B-ALL DI: Patients receive DI therapy comprising vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; 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 QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI. (CLOSED 03/19/2018)

MAINTENANCE THERAPY (M):

ARM A HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018)

GROUP II: VHR B-ALL: Patients are randomized to 1 of 3 treatment arms. (RANDOMIZATION CLOSED 02/15/2017)

CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY PART II:

ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL C (EXPERIMENTAL ARM 1): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017)

ARM C VHR B-ALL C (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (CLOSED 9/12/2014)

INTERIM MAINTENANCE THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY PART II:

ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL DI (EXPERIMENTAL ARM 1): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017)

ARM C VHR B-ALL DI (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014)

INTERIM MAINTENANCE THERAPY PART II: In all arms, patients receive vincristine sulfate IV over 1 minute and 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. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

GROUP III: PH-LIKE PREDICTED TKI-SENSITIVE KINASE MUTATION:

CONSOLIDATION THERAPY: Patients receive dasatinib PO QD on days 1-56, 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, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15 and 22 (days 1 and 8 only for CNS3 patients), vincristine sulfate IV over 1 minute on days 15, 22, 43 and 50, and pegaspargase IV over 1-2 hours on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY I: Patients receive dasatinib PO QD on days 1-63, vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29, and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

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

INTERIM MAINTENANCE THERAPY II: Patients dasatinib PO QD on days 1-56, vincristine sulfate IV over 1 minute 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, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours days 2 and 22.

MAINTENANCE THERAPY: Patients receive dasatinib PO QD on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29 and 57, prednisone PO BID or IV on days 1-5, 29-33 and 57-61, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78 (omit on days when MTX [IT] is given), mercaptopurine PO on days 1-84, methotrexate IT on day 1 (also day 29 of course 1 and 2, for patients who did not receive CNS radiation). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

Participants with Down syndrome are assigned to DS HR B-ALL:

INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

RAPID EARLY RESPONDERS (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

SLOW EARLY RESPONDERS (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: All 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; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 2-3, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: 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 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39.

MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

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

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Childrens Oncology Group

Principal Investigator
Michael James Burke

Trial IDs

Primary ID AALL1131
Secondary IDs NCI-2011-03797, CDR0000706370, NCT01406756, COG-AALL1131, S12-01254
Clinicaltrials.gov ID NCT02883049