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A Study to Compare Blinatumomab Alone to Blinatumomab with Nivolumab in Patients Diagnosed with First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Trial Status: Active

This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) that has come back (relapsed). Down syndrome patients with relapsed B-ALL are included in this study. Blinatumomab is an antibody, which is a protein that identifies and targets specific molecules in the body. Blinatumomab searches for and attaches itself to the cancer cell. Once attached, an immune response occurs which may kill the cancer cell. Nivolumab is a medicine that may boost a patient’s immune system. Giving nivolumab in combination with blinatumomab may cause the cancer to stop growing for a period of time, and for some patients, it may lessen the symptoms, such as pain, that are caused by the cancer.

Inclusion Criteria

  • Patients must be >= 1 and < 31 years at time of enrollment
  • Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories: * Isolated bone marrow relapse * Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse * Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes
  • Patients with Down syndrome (DS) are eligible in the following categories: * Isolated bone marrow relapse * Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular 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
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study * Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression * Radiation therapy (RT): >= 3 months must have elapsed if prior RT. This includes any patient requiring urgent radiation to any sites of extramedullary disease prior to enrollment (e.g. retinal/optic nerve involvement) * Hematopoietic stem cell transplant (HSCT): Patients must not have had a prior hematopoietic stem cell transplant * A single intrathecal chemotherapy at the time of relapse will be allowed. If < 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted * In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroid and/or hydroxyurea only) is permissible ** Group 1 and Down syndrome patients who received pre-enrollment therapy and have a white blood count (WBC) >= 30,000/ul at the time of enrollment must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no “washout” is required ** Group 1 and Down syndrome patients who received pre-enrollment therapy and have a WBC < 30,000/ul at the time of enrollment must be given a 24 hour “washout” before starting immunotherapy * Note: There is no waiting period or “washout” for patients who relapse while receiving upfront therapy
  • 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 (within 5 calendar days prior to enrollment): * Age: Maximum serum creatinine (mg/dL) ** 1 to < 2 years: 0.6 (male), 0.6 (female) ** 2 to < 6 years: 0.8 (male), 0.8 (female) ** 6 to < 10 years: 1 (male), 1 (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)
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
  • 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

Exclusion Criteria

  • Patients with B-lymphoblastic lymphoma (B-LLy)
  • Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
  • Patients with Philadelphia chromosome positive (Ph+) B-ALL
  • Patients with mixed phenotype acute leukemia (MPAL)
  • Patients with known Charcot-Marie-Tooth disease
  • Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype
  • Patients with active, uncontrolled infection defined as: * Positive bacterial blood culture within 48 hours of study enrollment * Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline. * Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed as long as blood cultures are negative for > 48 hours * A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection * Active viral or protozoal infection requiring IV treatment
  • Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible
  • Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement * Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are 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 an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Group 1 and DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible * Note: Group 2 and 3 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible provided that this is NOT the only site of relapsed disease
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab. Men receiving nivolumab and who are sexually active with WOCBP must continue contraception for 7 months after the last dose of nivolumab
  • Lactating females are not eligible unless they agree not to breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose

Alabama

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

Alaska

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

Arizona

Kingman
Kingman Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Mesa
Banner Children's at Desert
Status: ACTIVE
Contact: Site Public Contact
Phone: 480-412-3100
Tucson
Banner University Medical Center - Tucson
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Arkansas

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

California

Anaheim
Kaiser Permanente-Anaheim
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-398-3996
Arroyo Grande
PCR Oncology
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Bellflower
Kaiser Permanente-Bellflower
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-398-3996
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
Fontana
Kaiser Permanente-Fontana
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-398-3996
Loma Linda
Loma Linda University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 909-558-4050
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: ACTIVE
Contact: Site Public Contact
Phone: 323-361-4110
Kaiser Permanente Los Angeles Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-398-3996
Mattel Children's Hospital UCLA
Status: ACTIVE
Contact: Site Public Contact
Phone: 310-825-6708
Madera
Valley Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 559-353-3000
Oakland
Kaiser Permanente-Oakland
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 714-509-8646
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-694-0012
Sacramento
Sutter Medical Center Sacramento
Status: ACTIVE
Contact: Site Public Contact
Phone: 415-209-2686
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 916-734-3089
San Diego
Kaiser Permanente-San Diego Zion
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-398-3996
Rady Children's Hospital - San Diego
Status: ACTIVE
Contact: Site Public Contact
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-827-3222
Torrance
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 310-222-3624

Colorado

Aurora
Children's Hospital Colorado
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-764-5056
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

District of Columbia

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

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: ACTIVE
Contact: Site Public Contact
Phone: 239-343-5333
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
Orlando
AdventHealth Orlando
Status: ACTIVE
Contact: Site Public Contact
Phone: 407-303-2090
Arnold Palmer Hospital for Children
Status: ACTIVE
Contact: Site Public Contact
Phone: 321-841-2008
Nemours Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 407-650-7715
Pensacola
Sacred Heart Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 850-416-4611
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 727-767-4784
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: ACTIVE
Contact: Site Public Contact
Phone: 813-357-0849
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
Savannah
Memorial Health University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 912-350-7887

Hawaii

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

Idaho

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

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-880-4562
University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: ACTIVE
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-226-4357
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

Iowa

Des Moines
Blank Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-241-8912
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

Louisiana

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

Maine

Scarborough
Maine Children's Cancer Program
Status: ACTIVE
Contact: Site Public Contact
Phone: 207-396-7581

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 410-955-8804
Sinai Hospital of Baltimore
Status: ACTIVE
Contact: Site Public Contact
Phone: 410-601-6120
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: ACTIVE
Contact: Site Public Contact
Phone: 617-636-5535

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-865-1125
Battle Creek
Bronson Battle Creek
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Dearborn
Beaumont Hospital - Dearborn
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 248-551-7695
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: ACTIVE
Contact: Site Public Contact
Phone: 616-391-1230
Mercy Health Saint Mary's
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Spectrum Health at Butterworth Campus
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Kalamazoo
Borgess Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Bronson Methodist Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
West Michigan Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Muskegon
Mercy Health Mercy Campus
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Niles
Lakeland Hospital Niles
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Norton Shores
Cancer and Hematology Centers of Western Michigan - Norton Shores
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Reed City
Spectrum Health Reed City Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Royal Oak
Beaumont Children's Hospital-Royal Oak
Status: ACTIVE
Contact: Site Public Contact
Phone: 248-551-7695
William Beaumont Hospital-Royal Oak
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 248-551-7695
Saint Joseph
Lakeland Medical Center Saint Joseph
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Marie Yeager Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Traverse City
Munson Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230
Troy
William Beaumont Hospital - Troy
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 248-551-7695
Wyoming
Metro Health Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 616-391-1230

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
Cardinal Glennon Children's Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-268-4000
Mercy Hospital Saint Louis
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-251-7066
Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-600-3606

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

Nevada

Carson City
Carson Tahoe Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Henderson
Comprehensive Cancer Centers of Nevada - Henderson
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Henderson
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at Seven Hills
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Ann M Wierman MD LTD
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Central Valley
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Northwest
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Town Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Summerlin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Hope Cancer Care of Nevada
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at Charleston
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at Fort Apache
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at MountainView
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Pahrump
Hope Cancer Care of Nevada-Pahrump
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Reno
Cancer Care Specialists - Reno
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Renown Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013
Saint Mary's Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 702-384-0013

New Hampshire

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

New Jersey

Hackensack
Hackensack University Medical Center
Status: WITHDRAWN
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
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-7356
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-8675
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: ACTIVE
Contact: Site Public Contact
Phone: 973-754-2207

New York

Albany
Albany Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 518-262-5513
Bronx
Montefiore Medical Center - Moses Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 718-379-6866
Brooklyn
Maimonides Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 718-765-2500
Mineola
NYU Winthrop Hospital
Status: ACTIVE
Contact: Site Public Contact
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 212-639-7592
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 212-305-6361
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

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-9376
Durham
Duke University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-275-3853
Greenville
East Carolina University
Status: ACTIVE
Contact: Site Public Contact
Phone: 252-744-1015
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: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 701-323-5760

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
Cleveland
Cleveland Clinic Foundation
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-223-8100
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
Dayton
Dayton Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-228-4055
Sylvania
ProMedica Flower Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 419-824-1842
Toledo
ProMedica Toledo Hospital / Russell J Ebeid 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

Oregon

Portland
Oregon Health and Science University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 503-494-1080

Pennsylvania

Philadelphia
Children's Hospital of Philadelphia
Status: ACTIVE
Contact: Site Public Contact
Phone: 267-425-5544
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: ACTIVE
Contact: Site Public Contact
Phone: 412-692-8570

Puerto Rico

San Juan
University Pediatric Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 787-474-0333

Rhode Island

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

South Carolina

Columbia
Prisma Health Richland Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-241-6251
Greenville
BI-LO Charities Children's Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-241-6251

South Dakota

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

Tennessee

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
Corpus Christi
Driscoll Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 361-694-5311
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: ACTIVE
Contact: Site Public Contact
Phone: 214-648-7097
El Paso
El Paso Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 915-298-5444
Fort Worth
Cook Children's Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 682-885-2103
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 713-798-1354
San Antonio
Children's Hospital of San Antonio
Status: ACTIVE
Contact: Site Public Contact
Methodist Children's Hospital of South Texas
Status: ACTIVE
Contact: Site Public Contact
Phone: 210-575-6240
University of Texas Health Science Center at San Antonio
Status: ACTIVE
Contact: Site Public Contact
Phone: 210-450-3800

Utah

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

Virginia

Falls Church
Inova Fairfax Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 703-208-6650
Norfolk
Children's Hospital of The King's Daughters
Status: ACTIVE
Contact: Site Public Contact
Phone: 757-668-7243

Washington

Bellevue
Overlake Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 425-688-5407
Renton
Valley Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 425-228-3440
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-228-6618
Tacoma
Madigan Army Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 253-968-0129
Mary Bridge Children's Hospital and Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 253-403-1461
Yakima
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 509-574-3535

West Virginia

Bridgeport
United Hospital Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374
Martinsburg
WVUH-Berkely Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374
Morgantown
West Virginia University Healthcare
Status: ACTIVE
Contact: Site Public Contact
Phone: 304-293-7374
Parkersburg
Camden Clark Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-622-8922
Milwaukee
Children's Hospital of Wisconsin
Status: ACTIVE
Contact: Site Public Contact
Phone: 414-955-4727

Nova Scotia

Halifax
IWK Health Centre
Status: ACTIVE
Contact: Site Public Contact
Phone: 902-470-8037

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
Randwick
Sydney Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (02) 9382-1721
Westmead
The Children's Hospital at Westmead
Status: ACTIVE
Contact: Site Public Contact
Phone: 61-2-9845 1400

PRIMARY OBJECTIVES:

I. To compare rate of minimal residual disease (MRD) negative second remission (Rem-2) after up to two cycles of reinduction with blinatumomab versus (vs.) blinatumomab/nivolumab in Group 1 patients aged >= 1 to < 31 years old with first relapse of CD19+ B-ALL.

II. To compare event-free survival (EFS) PI (EFS post-induction) between consolidation with blinatumomab vs. blinatumomab/nivolumab in Group 3 patients aged >= 1 to <31 years old with first relapse of CD19+ B ALL.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of blinatumomab/nivolumab in patients aged >= 1 to < 31 years old with first relapse of CD19+ B ALL.

II. To compare EFS post-induction between blinatumomab vs. blinatumomab/nivolumab in Group 2 patients aged >= 1 to < 31 years old with first relapse of CD19+ B ALL.

EXPLORATORY OBJECTIVES:

I. In Group 1 patients, compare EFS between blinatumomab monotherapy and blinatumomab/nivolumab arms as compared to similar patients treated on the predecessor trial AALL1331.

II. In Group 1 patients, compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab to similar patients treated with block 1 of cytotoxic chemotherapy on the predecessor trial AALL1331.

III. In Group 2 patients with MRD >= 0.1% after vincristine sulfate, dexamethasone, pegylated asparaginase, and doxorubicin hydrochloride (VXLD), compare MRD negative second remission (Rem-2) rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomab/nivolumab arms.

IV. In patients with Down syndrome (DS) with first relapse of B-ALL, describe the safety, tolerability and efficacy (as defined by MRD negative second remission, Rem-2) after up to two cycles of blinatumomab/nivolumab.

OUTLINE: Patients >= 18 years old with marrow +/- extramedullary (EM) relapse of any duration after initial diagnosis, or patients < 18 years old with marrow +/- EM relapse < 24 months after initial diagnosis are assigned to Group 1. Patients < 18 years old with marrow +/- EM relapse >= 24 months from initial diagnosis, or all isolated extramedullary (IEM) relapses >= 1 to < 31 years old are assigned to Groups 2-3 re-induction. Patients with DS are assigned to Arm G. NOTE: Patients in Group 1 and DS patients with white blood cells (WBC) >= 30,000/uL, CNS 2/3 disease, or testicular disease must first receive 1 of 3 pre-immunotherapy treatments.

PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC >= 30,000/uL: Patients receive methotrexate (MTX) intrathecally (IT) or cytarabine IT or intrathecal triple therapy (ITT) consisting of MTX, hydrocortisone sodium succinate, and cytarabine IT at the time of diagnostic lumbar puncture (LP) or on day 1 (if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy). Patients also receive dexamethasone intravenously (IV) or orally (PO) twice daily (BID) on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1. Patients with DS also receive leucovorin calcium PO or IV every 6 hours (q6h) for 2 doses on day 2 or at 24 and 30 hours after each MTX or ITT dose. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 8 and no later than Day 15.

PRE-IMMUNOTHERAPY TREATMENT FOR CNS 2/3 DISEASE: Patients receive MTX IT or cytarabine IT twice weekly (Q2W) for 5-7 doses or Intrathecal Triple Therapy (ITT) IT Q2W for 3-4 doses until patient is CNS 1. Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each MTX or ITT dose. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 24.

PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE: Patients receive MTX IT, cytarabine IT, or ITT IT on days 1 and 15 (day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy). Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT MTX or ITT dose. Males with testicular disease at relapse undergo radiation once daily (QD) for a total of 12 fractions over 12 days. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 22.

GROUP 1: Patients are randomized to Arm A or Arm B.

ARM A: Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2, MTX IT, cytarabine IT, or ITT IT on days 1 and 15 of cycle 1 (MTX on day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy), and MTX IT on days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

ARM B: Patients receive dexamethasone, blinatumomab, and MTX, cytarabine, or ITT as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

GROUPS 2-3 REINDUCTION: Patients receive vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, 15, and 22, dexamethasone PO or IV on days 1-14, doxorubicin hydrochloride IV over 1-15 minutes on day 1, MTX IT on days 1, 8, and 29 (day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy) (days 8 and 29 for CNS 1/2 patients at relapse only), pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2 and 16, cytarabine IT on days 4 and 11 (CNS 2 patients at relapse only), then Q2W until 3 consecutive samples are clear of blasts, and ITT IT on days 8, 15, 22, and 29 (CNS 3 patients at relapse only). Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP 2: The following patients are randomized to Arm C or Arm D: 1) >= 1 to < 31 years old, IEM relapse < 18 months from diagnosis, regardless of MRD after Re-Induction. 2) < 18 years old with marrow relapse >= 24 to < 36 months from diagnosis regardless of MRD after Re-Induction, 3) >= 1 to < 31 years old, IEM relapse >= 18 months, and MRD >= 0.1% after Re-Induction, 4) < 18 years old with marrow relapse >= 36 months, and MRD >= 0.1% after Re-Induction.

ARM C: Patients receive dexamethasone PO or IV on day 1 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2, and MTX IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal MTX is given < 7 days prior to the start of cycle 1 ). Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

ARM D: Patients receive dexamethasone, blinatumomab, and MTX as in Arm C. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD < 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD >= 0.01% after cycle 1 proceed to cycle 2.

GROUP 3: The following patients are randomized to Arm E or Arm F: 1) >= 1 to < 31 years old with IEM relapse >= 18 months from diagnosis and MRD < 0.1% after Re-Induction, 2) < 18 years old with marrow relapse >= 36 months from diagnosis and MRD < 0.1% after Re-Induction.

ARM E:

IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (day 1 may be omitted from cycle 1 if intrathecal therapy is given < 7 days prior to the start of this cycle).Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2.

CONTINUATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, MTX PO on days 8, 15, 29, and 36, cyclophosphamide IV over 15-30 minutes on days 43 and 50, etoposide IV over 90-120 minutes on days 43 and 50, thioguanine PO once daily (QD) on days 43-49, and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 44-47 and 51-54. CNS 1/2 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22, and leucovorin calcium PO q6h for 2 doses on day 24. CNS 3 patients at relapse also receive ITT IT on days 1 and 43, intermediate dose MTX IV over 36 hours on day 22, and leucovorin calcium IV or PO q6h on days 24 and 25. Treatment repeats every 8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity.

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15.

MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity.

MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS ONLY): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments.

ARM F:

IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11-25 of cycle 1 and on days 1 and 15 of cycles 2 and 3, and MTX IT on days 1 and 15 (day 1 may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2.

CONTINUATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, MTX PO on days 8, 15, 29, and 36, cyclophosphamide IV over 15-30 minutes on days 43 and 50, etoposide IV over 90-120 minutes on days 43 and 50, thioguanine PO QD on days 43-49, and cytarabine IV over 1-30 minutes or SC on days 44-47 and 51-54. CNS 1/2 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22, and leucovorin calcium PO q6h for 2 doses on day 24. CNS 3 patients at relapse also receive ITT IT on days 1 and 43, intermediate dose MTX IV over 36 hours on day 22, and leucovorin calcium IV or PO q6h on days 24 and 25.

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15.

MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity.

MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3D-CRT over 5 days per week for a total of 10 treatments in the absence of disease progression or unacceptable toxicity.

ARM G (DS PATIENTS): Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2, and MTX IT, cytarabine IT, or ITT IT on days 1 and 15 of cycle 1 (MTX on day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of protocol therapy), MTX IT on days 1 and 15 of cycle 2, and leucovorin calcium IV or PO q6h for 2 doses on days 2 and 16.

Patients with MRD < 0.01% are eligible to come off protocol therapy to receive Consolidation therapy at the end of Cycle 1, or may choose to proceed to Arm G, Cycle 2.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Stacy L. Cooper

  • Primary ID AALL1821
  • Secondary IDs NCI-2020-06813
  • Clinicaltrials.gov ID NCT04546399