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Blinatumomab in Treating Younger Patients with Relapsed B-cell Acute Lymphoblastic Leukemia

Trial Status: Closed to Accrual

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia.

Inclusion Criteria

  • First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
  • No waiting period for patients who relapse while receiving standard maintenance therapy
  • Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status
  • Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue
  • Patient has not had prior treatment with blinatumomab
  • With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: * 1 to < 2 years: =< 0.6 mg/dL * 2 to < 6 years: =< 0.8 mg/dL * 6 to < 10 years: =< 1 mg/dL * 10 to < 13 years: =< 1.2 mg/dL * 13 to < 16 years: =< 1.5 mg/dL (males) and =< 1.4 mg/dL (females) * >= 16 years: =< 1.7 mg/dL (males) and =< 1.4 mg/dL (females)
  • Direct bilirubin < 3.0 mg/dL
  • Shortening fraction of >= 27% by echocardiogram, or
  • Ejection fraction of >= 50% by radionuclide angiogram
  • All patients and/or their parent or legal guardian 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

Exclusion Criteria

  • Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
  • Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
  • Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
  • Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
  • Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
  • Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
  • Patients with known human immunodeficiency virus (HIV) infection
  • Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
  • Lactating females who plan to breastfeed
  • 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
  • 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 pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
  • Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)

Alabama

Birmingham
Children's Hospital of Alabama
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 205-638-9285
Mobile
USA Health Strada Patient Care Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-388-8721

Alaska

Anchorage
Providence Alaska Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 907-212-6871

Arizona

Mesa
Banner Children's at Desert
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 602-747-9738
Phoenix
Phoenix Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 602-546-0920
Tucson
Banner University Medical Center - Tucson
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Arkansas

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

California

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

Colorado

Aurora
Children's Hospital Colorado
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 303-764-5056
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 303-839-6000

Connecticut

Hartford
Connecticut Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 860-545-9981
New Haven
Yale University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 203-785-5702

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 302-651-6884

District of Columbia

Washington
Children's National Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 202-884-2549

Florida

Fort Lauderdale
Broward Health Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 954-355-5346
Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 239-343-5333
Gainesville
University of Florida Health Science Center - Gainesville
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 352-273-8010
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 954-265-1847
Email: OHR@mhs.net
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 904-697-3529
Loxahatchee
Palms West Radiation Therapy
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
AdventHealth Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 407-303-2090
Arnold Palmer Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 321-843-2584
Pensacola
Nemours Children's Clinic - Pensacola
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 727-767-4784
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 813-356-7168
Tampa General Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 813-844-7829
West Palm Beach
Saint Mary's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 561-881-2815

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 404-785-2025
Savannah
Memorial Health University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 912-350-7887

Hawaii

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

Idaho

Boise
Saint Luke's Cancer Institute - Boise
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 208-381-2774

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 773-880-4562
University of Chicago Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 847-723-7570
Park Ridge
Advocate Children's Hospital-Park Ridge
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Peoria
Saint Jude Midwest Affiliate
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-226-4343
Springfield
Southern Illinois University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 317-338-2194

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 502-629-5500

Louisiana

New Orleans
Ochsner Medical Center Jefferson
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 504-703-8712

Maine

Bangor
Eastern Maine Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 207-973-4274
Scarborough
Maine Children's Cancer Program
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 207-396-7581

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 410-955-8804
Sinai Hospital of Baltimore
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 410-601-6120
University of Maryland / Greenebaum Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-888-8823
Bethesda
Walter Reed National Military Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Tufts Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 617-636-5535
Springfield
Baystate Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 413-794-3565
Worcester
UMass Memorial Medical Center - University Campus
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 508-856-3216

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-865-1125
Detroit
Ascension Saint John Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Wayne State University / Karmanos Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 313-576-9790
East Lansing
Michigan State University Clinical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 517-975-9547
Flint
Hurley Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Royal Oak
Beaumont Children's Hospital-Royal Oak
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 248-551-7695

Minnesota

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

Mississippi

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

Missouri

Kansas City
Children's Mercy Hospitals and Clinics
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu
Saint Louis
Mercy Hospital Saint Louis
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 314-251-7066
Washington University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 402-955-3949
University of Nebraska Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 402-559-6941

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-639-6918

New Jersey

Hackensack
Hackensack University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: 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: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 732-235-8675
Saint Peter's University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 732-745-8600ext6163
Newark
Newark Beth Israel Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 973-926-7230
Paterson
Saint Joseph's Regional Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 973-754-2207

New York

Albany
Albany Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 518-262-5513
Bronx
Montefiore Medical Center - Moses Campus
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 718-379-6866
Buffalo
Roswell Park Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-767-9355
Mineola
NYU Winthrop Hospital
Status: 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: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 718-470-3460
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-263-4434
Mount Sinai Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-824-7309
Email: CCTO@mssm.edu
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-305-6361
NYP / Weill Cornell Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-746-1848
Rochester
University of Rochester
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 585-275-5830
Stony Brook
Stony Brook University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-862-2215
Syracuse
State University of New York Upstate Medical University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 315-464-5476
Valhalla
New York Medical College
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 828-213-4150
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-804-9376
Novant Health Presbyterian Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 704-384-5369
Durham
Duke University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-275-3853
Greenville
East Carolina University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 252-744-1015
Winston-Salem
Wake Forest University Health Sciences
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 513-636-2799
Cleveland
Cleveland Clinic Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-223-8100
Rainbow Babies and Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 614-072-2657
Dayton
Dayton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-228-4055
Toledo
ProMedica Toledo Hospital / Russell J Ebeid Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 405-271-8777

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 503-413-2560
Oregon Health and Science University
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 503-494-1080

Pennsylvania

Allentown
Lehigh Valley Hospital-Cedar Crest
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Bethlehem
Lehigh Valley Hospital - Muhlenberg
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Danville
Geisinger Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 570-271-5251
Philadelphia
Children's Hospital of Philadelphia
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 267-425-5544
Saint Christopher's Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 215-427-8991
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 412-692-8570

Puerto Rico

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

Rhode Island

Providence
Rhode Island Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 401-444-1488

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 843-792-9321
Greenville
BI-LO Charities Children's Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 864-522-2066

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 605-312-3320

Tennessee

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

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 512-628-1902
Corpus Christi
Driscoll Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 361-694-5311
Dallas
Medical City Dallas Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 214-648-7097
El Paso
El Paso Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 915-298-5444
Fort Worth
Cook Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 682-885-2103
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 713-798-1354
Lubbock
Covenant Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
San Antonio
Children's Hospital of San Antonio
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Methodist Children's Hospital of South Texas
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 210-575-6240
Temple
Scott and White Memorial Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 254-724-5407

Utah

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

Virginia

Charlottesville
University of Virginia Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 434-243-6303
Falls Church
Inova Fairfax Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 703-208-6650
Norfolk
Children's Hospital of The King's Daughters
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 757-066-8724
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 804-628-1939
Roanoke
Carilion Children's
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 540-266-6238

Washington

Seattle
Seattle Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-228-6618
Tacoma
Madigan Army Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 253-968-0129

West Virginia

Charleston
West Virginia University Charleston Division
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-388-9944
Morgantown
West Virginia University Healthcare
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

Green Bay
Saint Vincent Hospital Cancer Center Green Bay
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 920-433-8889
Marshfield
Marshfield Medical Center-Marshfield
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-782-8581
Milwaukee
Children's Hospital of Wisconsin
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 414-955-4727

British Columbia

Vancouver
British Columbia Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 604-875-2345ext6477

Manitoba

Winnipeg
CancerCare Manitoba
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-561-1026

Newfoundland and Labrador

Saint John's
Janeway Child Health Centre
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-722-1126

Nova Scotia

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

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 905-521-2100
Kingston
Kingston Health Sciences Centre
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 613-549-6666
London
Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 519-685-8306
Ottawa
Children's Hospital of Eastern Ontario
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 613-738-3931
Toronto
Hospital for Sick Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 416-813-7654ext2027

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 514-412-4445
Quebec
Centre Hospitalier Universitaire de Quebec
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 418-525-4444

Saskatchewan

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

Australia

Perth
Perth Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Princess Margaret Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (08) 9340 8222

New Zealand

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

PRIMARY OBJECTIVES:

I. To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization). (Closed to enrollment effective September 18, 2019)

II. To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). (Closed to enrollment effective September 30, 2019)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization).

II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization).

EXPLORATORY OBJECTIVES:

I. To compare the rates of minimal residual disease (MRD) >= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization.

II. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab.

III. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD).

IV. To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness.

OUTLINE:

All patients receive Block 1 over 4 weeks.

BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2, and methotrexate intrathecally (IT) on day 1. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 or isolated CNS relapse also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2.

RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms. Effective 09/18/2019, HR/IR patients not yet randomized are not eligible for post-Induction therapy on AALL1331 and will be removed from protocol therapy. Patients receiving therapy on Arm A prior to Amendment #10A who have not yet received day 22 treatment on Block 3 will be offered the opportunity to cross over to Arm B to receive blinatumomab.

ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the Block 2.

ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the first block of blinatumomab.

RANDOMIZATION R2 (LR patients): Patients are then randomized to 1 of 2 treatment arms.

ARM C: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance. CNS3 patients receive chemoradiation post-Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2.

ARM D: Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance. CNS3 patients receive chemoradiation post Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2.

BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 10-11; pegaspargase IV over 1-2 hours on day 9 or 10; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22.

BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) or IV over 1 hour on days 2, 4, 9, 11, and 23; methotrexate IT on day 1and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 24-25. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 22.

BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29.

BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29.

BLINATUMOMAB BLOCK 3: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1.

CONTINUATION 1 & 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; or; cyclophosphamide IV over 15-30 minutes on days 43 and 50; etoposide IV over 1-2 hours on days 43 and 50; thioguanine PO once daily on days 43-49; and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 44-47 and 51-54. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43, methotrexate PO every 6 hours for 4 doses on day 22, leucovorin calcium PO every 6 hours for 2 doses on day 24. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43 ; methotrexate IV over 36 hours on day 22; and leucovorin calcium IV or PO every 6 hours on days 24-25.

MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. Cycles repeat every 12 weeks for up to 2 years since the beginning of treatment in the absence of disease progression or unacceptable toxicity.

MAINTENANCE CHEMORADIATION (LR CNS3 PATIENTS ONLY): Following maintenance cycle 1, patients receive 1800 cGy cranial radiation; dexamethasone PO BID or IV on days 1-7 and 15-21; vincristine sulfate IV over 1 minute on days 1, 8 and 15; and pegaspargase IV over 1-2 hours on day 1. Patients then resume maintenance with cycle 2 and beyond.

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

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Patrick A. Brown

  • Primary ID AALL1331
  • Secondary IDs NCI-2014-00631, COG-AALL1331, s15-00970
  • Clinicaltrials.gov ID NCT02101853