Imatinib Mesylate and Combination Chemotherapy in Treating Patients with Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Status: Active

Description

This randomized phase III trial studies how well imatinib mesylate and combination chemotherapy work in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 imatinib mesylate and combination chemotherapy may work better in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia.

Eligibility Criteria

Inclusion Criteria

  • For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled * For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe * In addition, laboratory reports detailing evidence of BCR-ABL1 fusion must be submitted for rapid central review within 72 hours of study enrollment
  • Newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
  • Patient must have previously started induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
  • Patient has not received more than 14 days of multiagent induction therapy beginning with the first dose of vinCRIStine
  • Patient may have started imatinib prior to study entry but has not received more than 14 days of imatinib
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
  • Direct bilirubin =< 2.0 mg/dL
  • Shortening fraction of >= 27% by echocardiogram
  • Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
  • Corrected QT interval, QTc < 480 msec * Note: Repeat echocardiogram is not required if echocardiogram was obtained within 21 days of study enrollment
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2
  • Serum creatinine within normal limits based on age/gender, as follows: * 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female) * 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female) * 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female) * 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female) * 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female) * >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)

Exclusion Criteria

  • Known history of chronic myelogenous leukemia (CML)
  • ALL developing after a previous cancer treated with cytotoxic chemotherapy
  • Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
  • Down syndrome
  • Pregnancy and breast feeding * 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
  • Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
  • Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinib
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Locations & Contacts

Alabama

Birmingham
Children's Hospital of Alabama
Status: Active
Contact: Site Public Contact
Phone: 205-638-9285
Email: oncologyresearch@peds.uab.edu

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
Madera
Valley Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 559-353-3000
Email: Research@valleychildrens.org
Oakland
Children's Hospital and Research Center at Oakland
Status: Active
Contact: Site Public Contact
Phone: 510-428-3324
Email: cgolden@mail.cho.org
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
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

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

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 Lauderdale
Broward Health Medical Center
Status: Active
Contact: Site Public Contact
Phone: 954-355-5346
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
Nicklaus Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 888-624-2778
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 305-243-2647
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
Pensacola
Sacred Heart Hospital
Status: Active
Contact: Site Public Contact
Phone: 850-416-4611
Email: eebrou@ascension.org
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
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 Illinois
Status: Active
Contact: Site Public Contact
Phone: 312-355-3046
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

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
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

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

Louisiana

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

Maine

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
Bethesda
Walter Reed National Military Medical Center
Status: Active
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 877-442-3324
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

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-865-1125
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
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 612-624-2620

Mississippi

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

Missouri

Kansas City
Children's Mercy Hospitals and Clinics
Status: Active
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu
Saint Louis
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
Paterson
Saint Joseph's Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 973-754-2207
Email: HallL@sjhmc.org

New Mexico

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

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Buffalo
Roswell Park Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-767-9355
Email: askroswell@roswellpark.org
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 / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-305-6361
Email: nr2616@cumc.columbia.edu
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

North Carolina

Asheville
Mission Hospital
Status: Active
Contact: Site Public Contact
Phone: 828-213-2539
Email: Karen.Smith3@HCAHealthcare.com
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
Novant Health Presbyterian Medical Center
Status: Active
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: 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
Columbus
Nationwide Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 614-072-2657
Email: amy.yekisa@nationwidechildrens.org
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
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
Danville
Geisinger Medical Center
Status: Active
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
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

Puerto Rico

Caguas
HIMA San Pablo Oncologic Hospital
Status: Active
Contact: Site Public Contact
Phone: 787-653-3434
San Juan
San Jorge Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 787-727-1000
University Pediatric Hospital
Status: Active
Contact: Site Public Contact
Phone: 787-474-0333

South Carolina

Charleston
Medical University of South Carolina
Status: Active
Contact: Site Public Contact
Phone: 843-792-9321
Email: hcc-clinical-trials@musc.edu
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
M D Anderson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-632-6789
Email: askmdanderson@mdanderson.org
Lubbock
Covenant Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
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

Utah

Salt Lake City
Primary Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 801-585-5270

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
Roanoke
Carilion Clinic Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 540-266-6238
Email: wpmccarty@carilionclinic.org

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
Madigan Army Medical Center
Status: Active
Contact: Site Public Contact
Phone: 253-968-0129
Email: mamcdci@amedd.army.mil
Mary Bridge Children's Hospital and Health Center
Status: Active
Contact: Site Public Contact
Phone: 253-403-1461
Email: research@multicare.org

West Virginia

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

Manitoba

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

Nova Scotia

Halifax
IWK Health Centre
Status: Active
Contact: Site Public Contact
Phone: 902-470-6767

Ontario

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

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: Active
Contact: Site Public Contact
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: Active
Contact: Site Public Contact
Phone: 514-412-4445
Email: info@thechildren.com
Quebec
Centre Hospitalier Universitaire de Quebec
Status: Active
Contact: Site Public Contact
Phone: 418-525-4444

Saskatchewan

Saskatoon
Saskatoon Cancer Centre
Status: Active
Contact: Site Public Contact
Phone: 306-655-2914

Australia

Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: (02) 4985 5180
Perth
Perth Children's Hospital
Status: Active
Contact: Site Public Contact
Email: helpdesk@childrensoncologygroup.org
Randwick
Sydney Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: (02) 9382-1721
South Brisbane
Queensland Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 61 7 3068 1111
Westmead
The Children's Hospital at Westmead
Status: Active
Contact: Site Public Contact
Phone: 61-2-9845 1400

New Zealand

Christchurch
Christchurch Hospital
Status: Active
Contact: Site Public Contact
Phone: 03 364 0640
Grafton
Starship Children's Hospital
Status: Active
Contact: Site Public Contact
Phone: 0800 728 436

Saudi Arabia

Riyadh
King Faisal Specialist Hospital and Research Centre
Status: Active
Contact: Site Public Contact
Phone: 011-966-1-464-7272 ext 38005

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To compare disease-free survival (DFS) of standard risk pediatric Philadelphia chromosome (Ph)+ acute lymphoblastic leukemia (ALL) treated with continuous imatinib mesylate (imatinib) combined with either a high-risk Children's Oncology Group (COG) ALL chemotherapy backbone or the more intensive European (Es)PhALL chemotherapy backbone.

SECONDARY OBJECTIVES:

I. To determine the feasibility of administration of imatinib after allogeneic hematopoietic stem cell transplantation (HSCT) in high risk Ph+ ALL patients.

II. To determine event-free survival (EFS) of high risk pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission and post-HSCT imatinib.

III. To compare rates of grade 3 or higher infections in standard risk (SR) Ph+ ALL patients between the two randomized arms.

IV. To evaluate event free survival (EFS) and overall survival (OS) of all enrolled participants.

V. To evaluate OS in SR patients.

VI. To evaluate OS in high risk (HR) patients.

EXPLORATORY OBJECTIVES:

I. To describe the toxicities associated with post-HSCT administration of imatinib.

II. To evaluate the long-term toxicities in SR patients treated with chemotherapy plus imatinib (no transplant), overall and between both randomized arms.

III. To determine prognostic significance of minimal residual disease (MRD) in Ph+ ALL at various time points during therapy.

IV. To evaluate MRD in HR patients just prior to HSCT and then at regular intervals post-HSCT and explore the association of these measurements with long-term outcome.

V. To evaluate concordance of MRD assessments made by IGH-T cell receptor (TCR) polymerase chain reaction (PCR) assay and next generation sequencing (NGS) assays.

VI. To determine prognostic significance of IKZF1 gene aberrations and deletions.

VII. To determine frequency and prognostic significance of p190 and p210 BCR-ABL1 fusion variants in pediatric Ph+ ALL.

VIII. To measure adherence to oral chemotherapeutic agents (imatinib, 6-mercaptopurine, and methotrexate) during the maintenance phase in SR Ph+ ALL patients.

IX. To identify factors associated with poor adherence.

X. To determine association between relapse risk and adherence to each oral chemotherapeutic agent (separately and combined).

XI. To measure adherence to imatinib after allogeneic HSCT in HR Ph+ ALL patients and identify factors associated with poor adherence.

OUTLINE:

INDUCTION IA PART 1: Patients receive induction IA according to standard of care on days 1-14.

INDUCTION IA PART 2: Patients receive imatinib mesylate orally (PO) once daily (QD) or twice daily (BID) on days 15-33, prednisolone PO twice daily (BID) or methylprednisolone intravenously (IV) on days 15-28, vincristine sulfate IV over 1 minute on days 15 and 22, daunorubicin hydrochloride IV over 1-15 minutes on days 15 and 22, and methotrexate intrathecally (IT) on day 29.

INDUCTION IB: Patients receive imatinib mesylate PO QD or BID on days 1-35, cyclophosphamide IV over 30-60 minutes on days 1 and 28, mercaptopurine PO on days 1-28, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 15-18, and 22-25, and methotrexate IT on days 8 and 22.

POST-INDUCTION THERAPY: Patients with standard risk are randomized to 1 of 2 arms. Patients with high risk are assigned to Arm C.

ARM A:

CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 6, dexamethasone PO BID or IV on days 1-5, cyclophosphamide IV over 30-60 minutes on days 2-4, leucovorin calcium PO or IV on days 3 and 4, high dose cytarabine IV over 3 hours and pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 5, and filgrastim SC on days 7-11 in the absence of disease progression or unexpected toxicity.

CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, dexamethasone PO BID or IV on days 1-5, vincristine sulfate IV over 1 minute on days 1 and 6, ifosfamide IV over 1 hour on days 2-4, leucovorin calcium PO or IV on days 3 and 4, dexrazoxane hydrochloride IV over 5-15 minutes and daunorubicin hydrochloride IV over 1-15 minutes on day 5, pegaspargase IV over 1-2 hours or IM on day 6, and filgrastim SC on days 7-11 in the absence of disease progression or unexpected toxicity.

CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate PO QD or BID on days 1-21, high dose cytarabine IV over 3 hours on days 1-2, dexamethasone PO BID or IV on days 1-5, etoposide IV over 1-2 hours on days 3-5, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 5, pegaspargase IV over 1-2 hours or IM on day 6, and filgrastim SC on days 7-11 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION 1 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 5-15 minutes, and doxorubicin IV over 1-15 minutes on days 8, 15, 22, and 29, and pegaspargase IV over 1-2 hours or IM on day 8 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION 1 PART 2: Patients receive imatinib mesylate PO QD on days 36-63, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 36-39 and 43-46, and methotrexate IT on days 36 and 43 in the absence of disease progression or unexpected toxicity.

INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate PO on days 1, 8, 15, and 22, and mercaptopurine PO on days 1-28 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION 2 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 5-15 minutes, and doxorubicin IV over 1-15 minutes on days 8, 15, 22, and 29, and pegaspargase IV over 1-2 hours or IM on day 8 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION 2 PART 2: Patients receive imatinib mesylate PO QD on days 36-49, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 36-39 and 43-46, and methotrexate IT on days 36 and 43 in the absence of disease progression or unexpected toxicity.

MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, methotrexate PO once weekly (QW) and IT on days 1 and 43 of cycles 1, 2, and 3, and mercaptopurine PO on days 1-84. Cycles with imatinib mesylate and mercaptopurine repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.

ARM B:

INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-63, vincristine sulfate IV over 1 minute and 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 on days 1-56, and methotrexate IT on days 1 and 29 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 5-15 minutes, and doxorubicin IV over 1-15 minutes on days 1, 8, and 15, and pegaspargase IV over 1-2 hours or IM on day 4 in the absence of disease progression or unexpected toxicity.

DELAYED INTENSIFICATION PART 2: Patients receive imatinib mesylate PO QD on days 29-56, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, 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 or IM on day 43 in the absence of disease progression or unexpected toxicity.

INTERIM MAINTENANCE WITH CAPIZZI METHOTREXATE: Patients receive imatinib mesylate PO QD or BID on days 1-56, vincristine sulfate IV over 1 minute and methotrexate IV over 2-15 minutes 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 in the absence of disease progression or unexpected toxicity.

MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29, and 57, prednisolone PO BID (or methylprednisolone IV for cycle 1 and 2) on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, methotrexate PO QW, and methotrexate IT on day 1 (and day 29 for cycle 1 and 2). Cycles repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.

ARM C:

CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, vincristine sulfate, dexamethasone, leucovorin calcium, high dose cytarabine, and pegaspargase as in Arm A Consolidation Block 1, and filgrastim SC on day 7 in the absence of disease progression or unexpected toxicity.

CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, dexamethasone, vincristine sulfate, ifosfamide, leucovorin calcium, dexrazoxane hydrochloride, daunorubicin hydrochloride, pegaspargase, and filgrastim as Arm A Consolidation Block 2 in the absence of disease progression or unexpected toxicity.

CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate, dexamethasone, etoposide, methotrexate, cytarabine, therapeutic hydrocortisone, pegaspargase, and filgrastim as in Arm A Consolidation Block 3, and high dose cytarabine IV over 3 hours on days 1-2 in the absence of disease progression or unexpected toxicity.

HSCT: Patients undergo HSCT on day 0. Patients who do not proceed to HSCT receive Delayed Intensification 1, Interim Maintenance, Delayed Intensification 2, and Maintenance as in Arm A.

POST-HSCT: Patients receive imatinib mesylate PO QD or BID starting on days 56-365 in the in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up every year for 3 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Childrens Oncology Group

Principal Investigator
Lewis Barry Silverman

Trial IDs

Primary ID AALL1631
Secondary IDs NCI-2016-01588
Clinicaltrials.gov ID NCT03007147