AzTrials
AzTrials

Down SyndromePhase 2NCT04546399

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

A Phase 2 study testing 3-Dimensional Conformal Radiation Therapy, Asparaginase Erwinia chrysanthemi and Biospecimen Collection in people with Down Syndrome and Recurrent B Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 227 sites in 4 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
3-Dimensional Conformal Radiation Therapy, Asparaginase Erwinia chrysanthemi and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
461 participants
Where
227 sitesin 4 countries
Study dates
17 Dec 2020to 30 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
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  • 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
  • Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay
  • 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
  • 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 (steroids and/or hydroxyurea only) is permissible
  • Patients with Down syndrome who received pre-enrollment therapy and have a white blood count (WBC) >= 30,000/ul at the time of enrollment still must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required
  • Patients with Down syndrome 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/sex as follows (within 7 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)
  • The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
  • 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

Who cannot join

  • 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 or ABL class Ph-like B-ALL (i.e. rearrangements involving ABL1, ABL2, CSF1R or PDGFRB and predicted to be sensitive to imatinib or dasatinib)
  • 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
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  • 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 if 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 if 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.
  • Patients with uncontrolled HIV, hepatitis B, or hepatitis C infection. 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
  • Patients with DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible
  • Note: Group 3 and 4 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if 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
  • Lactating females are not eligible unless they agree to not 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

Trial locations and contacts

227 sites in 4 countries. Contact the study team or a site near you to ask about taking part.

227 sites in 4 countries

United States211 sites, 152 recruiting

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

    Site Public Contact, 330-543-3193

    Erin Wright

    Recruiting

  • Albany Medical Center

    Albany, New York, 12208

    Site Public Contact, 518-262-5513

    Lauren R. Weintraub

    Recruiting

  • Presbyterian Hospital

    Albuquerque, New Mexico, 87106

    Site Public Contact, 505-559-6113, wburman@phs.org

    Beeling Armijo

    Recruiting

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

    Site Public Contact, 610-402-9543, Morgan_M.Horton@lvhn.org

    Jacob A. Troutman

    Recruiting

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

    Site Public Contact, 800-398-3996, clinical.trials@kp.org

    Robert M. Cooper

    Recruiting

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

    Suspended

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

    Site Public Contact, 800-865-1125

    Joshua W. Goldman

    Recruiting

  • PCR Oncology

    Arroyo Grande, California, 93420

    Suspended

  • Mission Hospital

    Asheville, North Carolina, 28801

    Site Public Contact, 828-213-7055, NCDV.ResearchRegulatory@HCAHealthcare.com

    Douglas J. Scothorn

    Recruiting

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

    Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org

    Waitman K. Aumann

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org

    Kelly E. Faulk

    Recruiting

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

    Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org

    Shannon M. Cohn

    Recruiting

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

    Site Public Contact, 410-601-9083

    Jason M. Fixler

    Recruiting

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

    Site Public Contact, 410-955-8804, jhcccro@jhmi.edu

    Stacy L. Cooper

    Recruiting

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

    Site Public Contact, 207-973-4274

    Daniel L. Callaway

    Recruiting

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

    Suspended

  • Overlake Medical Center

    Bellevue, Washington, 98004

    Suspended

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

    Suspended

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

    Active, not recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

    Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu

    Matthew A. Kutny

    Recruiting

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

    Site Public Contact, 208-381-2774, eslinget@slhs.org

    Martha M. Pacheco

    Recruiting

  • Tufts Children's Hospital

    Boston, Massachusetts, 02111

    Active, not recruiting

  • United Hospital Center

    Bridgeport, West Virginia, 26330

    Suspended

  • Maimonides Medical Center

    Brooklyn, New York, 11219

    Site Public Contact, 718-765-2500

    Mahmut Y. Celiker

    Recruiting

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

    Site Public Contact, 802-656-8990, rpo@uvm.edu

    Jessica L. Heath

    Recruiting

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

    Suspended

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

    Site Public Contact, 877-668-0683, cancerclinicaltrials@med.unc.edu

    Thomas B. Alexander

    Recruiting

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

    Site Public Contact, 304-388-9944

    Mohamad H. Badawi

    Recruiting

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

    Site Public Contact, 800-804-9376

    Joel A. Kaplan

    Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Jenna Rossoff

    Recruiting

  • University of Illinois

    Chicago, Illinois, 60612

    Site Public Contact, 312-355-3046

    Dipti S. Dighe

    Recruiting

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

    Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu

    Gabrielle Lapping-Carr

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Site Public Contact, 513-636-2799, cancer@cchmc.org

    Erin H. Breese

    Recruiting

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio, 44106

    Site Public Contact, 216-844-5437

    Duncan S. Stearns

    Recruiting

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

    Suspended

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Stuart L. Cramer

    Recruiting

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

    Site Public Contact, 614-722-6039, Melinda.Triplet@nationwidechildrens.org

    Mark A. Ranalli

    Recruiting

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

    Site Public Contact, 361-694-5311, Crystal.DeLosSantos@dchstx.org

    Nkechi I. Mba

    Recruiting

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

    Site Public Contact, 972-566-5588

    Maurizio L. Ghisoli

    Recruiting

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

    Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu

    Tamra L. Slone

    Recruiting

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

    Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu

    Jagadeesh Ramdas

    Recruiting

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

    Site Public Contact, 800-228-4055

    Jordan M. Wright

    Recruiting

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

    Suspended

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

    Site Public Contact, 303-832-2344, PSGResearchSharedMailbox@HCAHealthcare.com

    Florence Choo

    Recruiting

  • Blank Children's Hospital

    Des Moines, Iowa, 50309

    Site Public Contact, 515-241-8912, samantha.mallory@unitypoint.org

    Samantha L. Mallory

    Recruiting

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

    Suspended

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

    Site Public Contact, 626-564-3455

    Robert M. Cooper

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Active, not recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27710

    Site Public Contact, 888-275-3853

    Jessica M. Sun

    Recruiting

  • Michigan State University

    East Lansing, Michigan, 48823

    Active, not recruiting

  • El Paso Children's Hospital

    El Paso, Texas, 79905

    Site Public Contact, 915-298-5444, ranjan.bista@ttuhsc.edu

    Benjamin Carcamo

    Recruiting

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

    Site Public Contact, 703-208-6650, Stephanie.VanBebber@inova.org

    Robin Y. Dulman

    Recruiting

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

    Site Public Contact, 701-323-5760, OncologyClinicalTrialsFargo@sanfordhealth.org

    Samuel J. Milanovich

    Recruiting

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

    Site Public Contact, 800-398-3996, clinical.trials@kp.org

    Robert M. Cooper

    Recruiting

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

    Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org

    Emad K. Salman

    Recruiting

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

    Site Public Contact, 682-885-2103, CookChildrensResearch@cookchildrens.org

    Kenneth M. Heym

    Recruiting

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

    Site Public Contact, 352-273-8010

    Brian Stover

    Recruiting

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

    Suspended

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

    Suspended

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

    Site Public Contact, 920-433-8889, WI_research_admin@hshs.org

    Catherine A. Long

    Recruiting

  • East Carolina University

    Greenville, North Carolina, 27834

    Site Public Contact, 252-744-1015, eubankss@ecu.edu

    Andrea R. Whitfield

    Recruiting

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Aniket Saha

    Recruiting

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Aniket Saha

    Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Site Public Contact, 551-996-2897

    Jing Chen

    Recruiting

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

    Site Public Contact, 860-545-9981

    Michael S. Isakoff

    Recruiting

  • Comprehensive Cancer Centers of Nevada - Henderson

    Henderson, Nevada, 89052

    Suspended

  • Comprehensive Cancer Centers of Nevada-Horizon Ridge

    Henderson, Nevada, 89052

    Suspended

  • Las Vegas Cancer Center-Henderson

    Henderson, Nevada, 89052

    Suspended

  • Comprehensive Cancer Centers of Nevada-Southeast Henderson

    Henderson, Nevada, 89074

    Suspended

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

    Site Public Contact, 717-531-6012

    Lisa M. McGregor

    Recruiting

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

    Site Public Contact, 954-265-1847, OHR@mhs.net

    Iftikhar Hanif

    Recruiting

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

    Site Public Contact, 808-983-6090

    Wade T. Kyono

    Recruiting

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 713-798-1354, burton@bcm.edu

    Anil George

    Recruiting

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org

    Najat C. Daw

    Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

    Site Public Contact, 800-248-1199

    Sandeep Batra

    Recruiting

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

    Site Public Contact, 800-237-1225

    Andrew P. Groves

    Recruiting

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

    Site Public Contact, 601-815-6700

    Amanda Strobel

    Recruiting

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Emi H. Caywood

    Recruiting

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

    Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org

    Kathleen Y. Butler

    Recruiting

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

    Suspended

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

    Suspended

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

    Site Public Contact, 816-302-6808, COGResearchGroup@cmh.edu

    Keith J. August

    Recruiting

  • Kingman Regional Medical Center

    Kingman, Arizona, 86401

    Suspended

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

    Site Public Contact, 865-541-8266

    Susan E. Spiller

    Recruiting

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

    Suspended

  • Hope Cancer Care of Nevada

    Las Vegas, Nevada, 89103

    Suspended

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada, 89109

    Suspended

  • Ann M Wierman MD LTD

    Las Vegas, Nevada, 89128

    Suspended

  • Comprehensive Cancer Centers of Nevada - Northwest

    Las Vegas, Nevada, 89128

    Suspended

  • OptumCare Cancer Care at MountainView

    Las Vegas, Nevada, 89128

    Suspended

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

    Site Public Contact, 702-384-0013, research@sncrf.org

    Alan K. Ikeda

    Recruiting

  • Comprehensive Cancer Centers of Nevada - Town Center

    Las Vegas, Nevada, 89144

    Suspended

  • Comprehensive Cancer Centers of Nevada-Summerlin

    Las Vegas, Nevada, 89144

    Suspended

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada, 89144

    Site Public Contact, 702-384-0013, research@sncrf.org

    Alan K. Ikeda

    Recruiting

  • Las Vegas Cancer Center-Medical Center

    Las Vegas, Nevada, 89148-2405

    Suspended

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

    Suspended

  • Comprehensive Cancer Centers of Nevada - Central Valley

    Las Vegas, Nevada, 89169

    Suspended

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89183

    Suspended

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

    Site Public Contact, 800-639-6918, cancer.research.nurse@dartmouth.edu

    Angela Ricci

    Recruiting

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

    Site Public Contact, 859-257-3379

    James T. Badgett

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

    Site Public Contact, 501-364-7373

    Michael W. Bishop

    Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

    Site Public Contact, 909-558-4050

    Albert Kheradpour

    Recruiting

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

    Site Public Contact, 562-933-5600

    Jacqueline N. Casillas

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

    Site Public Contact, 323-361-4110

    Jamie L. Stokke

    Recruiting

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

    Suspended

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Site Public Contact, 310-423-2133, Cancer.trial.info@cshs.org

    Nicole M. Baca

    Recruiting

  • Mattel Children's Hospital UCLA

    Los Angeles, California, 90095

    Site Public Contact, 310-825-6708

    Satiro N. De Oliveira

    Recruiting

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

    Site Public Contact, 502-629-5500, CancerResource@nortonhealthcare.org

    Michael J. Ferguson

    Recruiting

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

    Site Public Contact, 806-725-8657, mbisbee@providence.org

    Kishor M. Bhende

    Recruiting

  • UMC Cancer Center / UMC Health System

    Lubbock, Texas, 79415

    Site Public Contact, 806-775-8590

    Erin K. Barr

    Recruiting

  • Valley Children's Hospital

    Madera, California, 93636

    Site Public Contact, 559-353-3000, Research@valleychildrens.org

    Ruetima Titapiwatanakun

    Recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Cathy A. Lee-Miller

    Recruiting

  • WVUH-Berkely Medical Center

    Martinsburg, West Virginia, 25401

    Suspended

  • Loyola University Medical Center

    Maywood, Illinois, 60153

    Site Public Contact, 708-226-4357

    Eugene Suh

    Recruiting

  • Banner Children's at Desert

    Mesa, Arizona, 85202

    Site Public Contact, 480-412-3100

    Joseph C. Torkildson

    Recruiting

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

    Site Public Contact, 414-955-4727, MACCCTO@mcw.edu

    Michael J. Burke

    Recruiting

  • NYU Langone Hospital - Long Island

    Mineola, New York, 11501

    Site Public Contact, 212-263-4432, cancertrials@nyulangone.org

    Chana L. Glasser

    Recruiting

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

    Site Public Contact, 612-813-5913, pauline.mitby@childrensmn.org

    Michael K. Richards

    Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

    Site Public Contact, 612-624-2620

    Peter M. Gordon

    Recruiting

  • USA Health Strada Patient Care Center

    Mobile, Alabama, 36604

    Site Public Contact, 800-388-8721

    Hamayun Imran

    Recruiting

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

    Site Public Contact, 304-293-7374, cancertrialsinfo@hsc.wvu.edu

    Ashley E. Meyer

    Recruiting

  • Morristown Medical Center

    Morristown, New Jersey, 07960

    Site Public Contact, 973-971-5900

    Kathryn L. Laurie

    Recruiting

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

    Suspended

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

    Site Public Contact, 615-342-1919

    Clinton M. Carroll

    Recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

    Site Public Contact, 800-811-8480

    Brianna N. Smith

    Recruiting

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

    Site Public Contact, 732-745-8600 ext. 6163, kcovert@saintpetersuh.com

    Nibal A. Zaghloul

    Recruiting

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

    Site Public Contact, 732-235-8675

    Richard A. Drachtman

    Recruiting

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

    Site Public Contact, 732-235-7356

    Richard A. Drachtman

    Recruiting

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

    Site Public Contact, 718-470-3460

    Julie I. Krystal

    Recruiting

  • Children's Hospital New Orleans

    New Orleans, Louisiana, 70118

    Site Public Contact, 504-894-5377

    Maria C. Velez-Yanguas

    Recruiting

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

    Active, not recruiting

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

    Suspended

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

    Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Nobuko Hijiya

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Kavitha Ramaswamy

    Recruiting

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

    Site Public Contact, 212-746-1848

    Jaclyn Rosenzweig

    Recruiting

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

    Site Public Contact, 973-926-7230, Christine.Kosmides@rwjbh.org

    Teena Bhatla

    Recruiting

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

    Suspended

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

    Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org

    Melissa S. Mark

    Recruiting

  • Cancer and Hematology Centers of Western Michigan - Norton Shores

    Norton Shores, Michigan, 49444

    Suspended

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

    Site Public Contact, 877-642-4691, Kpoct@kp.org

    Aarati V. Rao

    Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

    Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu

    Rene Y. McNall-Knapp

    Recruiting

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

    Site Public Contact, 402-955-3949

    Jill C. Beck

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Site Public Contact, 402-559-6941, unmcrsa@unmc.edu

    Jill C. Beck

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Site Public Contact, 714-509-8646, oncresearch@choc.org

    Elyssa M. Rubin

    Recruiting

  • AdventHealth Orlando

    Orlando, Florida, 32803

    Site Public Contact, 407-303-2090, FH.Cancer.Research@flhosp.org

    Fouad M. Hajjar

    Recruiting

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

    Site Public Contact, 321-841-5357, Jennifer.spinelli@orlandohealth.com

    Jaime M. Libes-Bander

    Recruiting

  • Nemours Children's Hospital

    Orlando, Florida, 32827

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Emi H. Caywood

    Recruiting

  • Hope Cancer Care of Nevada-Pahrump

    Pahrump, Nevada, 89048

    Suspended

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

    Site Public Contact, 800-694-0012, ccto-office@stanford.edu

    Jay Michael S. Balagtas

    Recruiting

  • Camden Clark Medical Center

    Parkersburg, West Virginia, 26101

    Suspended

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

    Site Public Contact, 973-754-2207, HallL@sjhmc.org

    Alissa Kahn

    Recruiting

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

    Site Public Contact, helpdesk@childrensoncologygroup.org

    Jeffrey H. Schwartz

    Recruiting

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

    Suspended

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

    Site Public Contact, 309-624-4945, ChildrensHospitalofIllinois@osfhealthcare.org

    Prerna Kumar

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu

    Shannon L. Maude

    Recruiting

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

    Site Public Contact, 215-427-8991

    Gregory E. Halligan

    Recruiting

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

    Site Public Contact, 602-546-0920

    Dana B. Salzberg

    Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

    Site Public Contact, 412-692-8570, jean.tersak@chp.edu

    Jenny Ruiz

    Recruiting

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

    Site Public Contact, 503-413-2560

    Jason M. Glover

    Recruiting

  • Oregon Health and Science University

    Portland, Oregon, 97239

    Site Public Contact, 503-494-1080, trials@ohsu.edu

    Bill H. Chang

    Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

    Site Public Contact, 401-444-1488

    Bradley DeNardo

    Recruiting

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

    Suspended

  • Renown Regional Medical Center

    Reno, Nevada, 89502

    Site Public Contact, 775-982-5050, Renown-CRD@renown.org

    Alan K. Ikeda

    Recruiting

  • Saint Mary's Regional Medical Center

    Reno, Nevada, 89503

    Suspended

  • Cancer Care Specialists - Reno

    Reno, Nevada, 89511

    Suspended

  • Valley Medical Center

    Renton, Washington, 98055

    Suspended

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

    Site Public Contact, 804-628-6430, CTOclinops@vcu.edu

    Jordyn R. Griffin

    Recruiting

  • University of Rochester

    Rochester, New York, 14642

    Active, not recruiting

  • Corewell Health Children's

    Royal Oak, Michigan, 48073

    Site Public Contact, 248-551-7695

    Marie V. Nelson

    Recruiting

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan, 48073

    Suspended

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

    Site Public Contact, clinicalresearch@sutterhealth.org

    Sandra Baril

    Recruiting

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Site Public Contact, 916-734-3089

    Marcio H. Malogolowkin

    Recruiting

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

    Suspended

  • Corewell Health Lakeland Hospitals - Saint Joseph Hospital

    Saint Joseph, Michigan, 49085

    Suspended

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Site Public Contact, 801-585-5270

    Luke D. Maese

    Recruiting

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

    Site Public Contact, 210-704-2894, bridget.medina@christushealth.org

    Julie Voeller

    Recruiting

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

    Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com

    Jose M. Esquilin

    Recruiting

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

    Site Public Contact, 210-450-3800, phoresearchoffice@uthscsa.edu

    Anne-Marie R. Langevin

    Recruiting

  • Kaiser Permanente-San Diego Zion

    San Diego, California, 92120

    Site Public Contact, 800-398-3996, clinical.trials@kp.org

    Robert M. Cooper

    Recruiting

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

    Site Public Contact, 858-966-5934

    William D. Roberts

    Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

    Site Public Contact, 877-827-3222, cancertrials@ucsf.edu

    Karen R. Rabin

    Recruiting

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

    Site Public Contact, 912-350-7887, Lorraine.OHara@hcahealthcare.com

    Andrew L. Pendleton

    Recruiting

  • Maine Children's Cancer Program

    Scarborough, Maine, 04074

    Site Public Contact, 207-396-8670, clinicalresearch@mainehealth.org

    Eric C. Larsen

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Site Public Contact, 866-987-2000

    Sarah E. Leary

    Recruiting

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

    Site Public Contact, 605-312-3320, OncologyClinicalTrialsSF@SanfordHealth.org

    Jordan Fritch-Hanson

    Recruiting

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

    Site Public Contact, 800-228-6618, HopeBeginsHere@providence.org

    Judy L. Felgenhauer

    Recruiting

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

    Site Public Contact, 314-268-4000

    William S. Ferguson

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Kristin Zorn

    Recruiting

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

    Site Public Contact, 314-251-7066

    Robin D. Hanson

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

    Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu

    Jennifer L. Mayer

    Recruiting

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

    Site Public Contact, 800-862-2215

    Laura E. Hogan

    Recruiting

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

    Suspended

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

    Site Public Contact, 315-464-5476

    Melanie A. Comito

    Recruiting

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

    Site Public Contact, 253-403-1461, research@multicare.org

    Robert G. Irwin

    Recruiting

  • Madigan Army Medical Center

    Tacoma, Washington, 98431

    Site Public Contact, 253-968-6144, melissa.a.forouhar.mil@health.mil

    Melissa A. Forouhar

    Recruiting

  • Tampa General Hospital

    Tampa, Florida, 33606

    Site Public Contact, 813-844-7829, syapchanyk@tgh.org

    Andrew J. Galligan

    Recruiting

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

    Site Public Contact, 813-357-0849, jennifer.manns@baycare.org

    Don E. Eslin

    Recruiting

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

    Site Public Contact, 718-379-6866, eskwak@montefiore.org

    Alice Lee

    Recruiting

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio, 43606

    Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org

    Jamie L. Dargart

    Recruiting

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

    Active, not recruiting

  • Munson Medical Center

    Traverse City, Michigan, 49684

    Suspended

  • Corewell Health Beaumont Troy Hospital

    Troy, Michigan, 48085

    Suspended

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

    Site Public Contact, UACC-IIT@uacc.arizona.edu

    Monica M. Davini

    Recruiting

  • Saint Francis Children's Hospital

    Tulsa, Oklahoma, 74136

    Site Public Contact, 918-502-6720

    Jill A. Salo

    Recruiting

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

    Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org

    Jeffrey S. Dome

    Recruiting

  • Saint Mary's Medical Center

    West Palm Beach, Florida, 33407

    Site Public Contact, 561-822-4745

    Matthew D. Ramirez

    Recruiting

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

    Site Public Contact, 302-651-5572, Allison.bruce@nemours.org

    Emi H. Caywood

    Recruiting

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

    Site Public Contact, 336-713-6771

    Sarah Supples

    Recruiting

  • University of Michigan Health - West

    Wyoming, Michigan, 49519

    Suspended

  • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

    Yakima, Washington, 98902

    Suspended

Other trials in United States

Canada10 sites, 1 recruiting

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

    Suspended

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2B7

    Suspended

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

    Suspended

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec, H3H 1P3

    Suspended

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

    Suspended

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

    Suspended

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec, J1H 5N4

    Suspended

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

    Site Public Contact, 709-777-8727, beverlyj.mitchell@easternhealth.ca

    Lisa A. Goodyear

    Recruiting

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

    Suspended

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

    Suspended

Other trials in Canada

Australia5 sites

  • John Hunter Children's Hospital

    Hunter Regional Mail Centre, New South Wales, 2310

    Suspended

  • Perth Children's Hospital

    Perth, Western Australia, 6009

    Suspended

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

    Suspended

  • Queensland Children's Hospital

    South Brisbane, Queensland, 4101

    Suspended

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

    Suspended

Other trials in Australia

Puerto Rico1 site, 1 recruiting

  • University Pediatric Hospital

    San Juan, 00926

    Site Public Contact, 787-474-0333

    Maria E. Echevarria

    Recruiting

Other trials in Puerto Rico

About this study

Official title: A Phase 2 Study of Blinatumomab (NSC# 765986) in Combination With Nivolumab (NSC# 748726), a Checkpoint Inhibitor of PD-1, in B-ALL Patients Aged &gt;/= 1 to &lt; 31 Years Old With First Relapse

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare event free survival post reinduction (EFS PR) between blinatumomab vs. blinatumomab/nivolumab in Group 4 patients aged ≥ 1 to <31 years old with first relapse of CD19+ B ALL.

II. To compare EFS PR (EFS post-reinduction) 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:

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

EXPLORATORY OBJECTIVES:

  1. In Group 4 patients, compare EFS PR between blinatumomab monotherapy and blinatumomab/nivolumab arms as compared to similar patients treated on the predecessor trial AALL1331.

II. In Group 4 patients, compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab.

III. In Group 4 patients, 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.

  1. With each Group, perform subset analyses of EFS and overall survival (OS) based on features including degree of marrow disease at relapse, age, sex, body mass index, cytogenetics, site(s) of relapse, percent peripheral blasts at relapse and absolute lymphocyte count at first relapse.

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.

Starting with amendment 4C (9/19/2024), patients with DS are assigned to group 3 or 4. Patients < 18 years with bone marrow first relapse ≥ 36 months from initial diagnosis with MRD <0.1% after VXLD reinduction or with isolated CNS/testicular extramedullary relapse occurring ≥ 18 months from initial diagnosis with MRD <0.1% after VXLD reinduction are assigned to group 3. Patients who do not meet criteria for group 3 will be assigned to group 4. Patients with Down syndrome ≥ 1 to < 31 years of age with first bone marrow relapse of B ALL are assigned to arm G.

PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC >= 30,000/uL (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G) : 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 via infusion or IV push over 1 minute 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 IT administration. 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 (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): 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 IT administration. 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(CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): 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 administration. 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 (CLOSED TO ACCRUAL 9/19/2024): 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, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given < 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 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 2-4 VXLD REINDUCTION: Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV on days 1-14, doxorubicin hydrochloride IV over 3-15 minutes on day 1, MTX IT on days 1, 8, and 29 (day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP < 7 days prior to the start of this cycle) (days 8 and 29 for CNS 1 patients at relapse only), pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2 and 16 or calaspargase IV over 1-2 hours on day 2 (for patients ≤ 22 years), 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). Patients with CNS 2 disease at relapse that does not resolve to CNS 1 by day 15 receive maintenance chemoradiation before initiation of maintenance. Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP 2 (CLOSED TO ACCRUAL 9/19/2024): 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: Patients are randomized to Arm E or Arm F.

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 Consolidation cycles 1-2.

CONSOLIDATION: Patients receive dexamethasone PO or IV on days 1-5, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only).

INTENSIFICATION 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, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia chrysanthemi IM on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only).

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (CNS 1/2 at relapse only) or ITT IT on days 1 and 15 (CNS 3 at relapse only).

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 (only for patients who did not receive cranial radiation), and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (Omit day 1 for patients receiving day 1 IT MTX). 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: Prior to the first cycle of maintenance therapy, patients with CNS 3 at relapse or CNS 2 at relapse that did not resolve to CNS 1 by day 15 of VXLD Reinduction 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 or calaspargase 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 of cycle 1 and on days 1 of cycles 2 and 3, and MTX IT on days 1 and 15 (CNS 1/2 patients at relapse only)(day 1 may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle) or , ITT IT on days 1 and 15 (CNS 3 patients at relapse only) (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 Consolidation cycles 1-2.

CONSOLIDATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only).

INTENSIFICATION 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, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia chrysanthemi IM on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only).

IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on day 1 and MTX IT on days 1 and 15 (CNS 1/2 at relapse only) or ITT IT on days 1 and 15 (CNS 3 at relapse only).

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 (only for patients who did not receive cranial radiation), and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 (Omit for patients receiving day 1 IT MTX). 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: Prior to the first cycle of maintenance therapy, patients with CNS 3 at relapse or CNS 2 at relapse that did not resolve to CNS 1 by day 15 of VXLD Reinduction 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 or calaspargase 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.

GROUP 4: Patients are randomized to arm H or arm I.

ARM H: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ARM I: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles 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 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD <0.01% at the end of Cycle 1 may stop study treatment at the discretion of the treating physician.

Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.

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

Being tested
3-Dimensional Conformal Radiation Therapy, Asparaginase Erwinia chrysanthemi, Biospecimen Collection, Blinatumomab, Bone Marrow Aspiration
Medical subject headings
Down Syndrome, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 3-Dimensional Conformal Radiation TherapyRadiation

    Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT

    Undergo 3D-CRT

  • Asparaginase Erwinia chrysanthemiDrug

    Also called Asparaginase Erwinia chrysanthemi (Recombinant)-rywn, Asparaginase Erwinia chrysanthemi, Recombinant-rywn, Asparaginase Erwinia chrysanthemi-rywn, Crisantaspase

    Given IM

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood, urine and cerebrospinal fluid collection

  • BlinatumomabBiological

    Also called AMG 103, AMG-103, AMG103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody

    Given IV

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Calaspargase PegolDrug

    Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IT

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO or IV

  • Hydrocortisone Sodium SuccinateDrug

    Also called (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan

    Given IT

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • MercaptopurineDrug

    Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine

    Given PO

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IT, PO, and IV

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • PegaspargaseDrug

    Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase

    Given IM or IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV push or via infusion

Study groups in NCT04546399
Study groupRoleWhat they receive
Arm G (dexamethasone, blinatumomab, nivolumab,MTX) DS patientsExperimentalPatients 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 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD <0.01% at the end of Cycle 1 may stop study treatment at the discretion of the treating physician. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate; Biological: Nivolumab
Group 1, Arm A (dexamethasone, blinatumomab, MTX)ExperimentalARM 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, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given < 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 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. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate
Group 1, Arm B (dexamethasone, blinatumomab, MTX)ExperimentalPatients 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. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate; Biological: Nivolumab
Group 2, Arm C (dexamethasone, blinatumomab, MTX)ExperimentalPatients 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 methotrexate IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal therapy is given < 7 days prior to the start of this cycle). 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. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Dexamethasone; Procedure: Lumbar Puncture; Drug: Methotrexate
Group 2, Arm D (dexamethasone, nivolumab, blinatumomab, MTX)ExperimentalPatients 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. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Dexamethasone; Procedure: Lumbar Puncture; Drug: Methotrexate; Biological: Nivolumab
Group 3, Arm E (dexamethasone, blinatumomab, MTX)ExperimentalSee Outline section
Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine Sulfate
Group 3, Arm F (dexamethasone, blinatumomab, nivolumab)ExperimentalSee Outline section
Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Biological: Nivolumab; Drug: Pegaspargase; Drug: Vincristine Sulfate
Group 4 Arm I (Dexamethasone, blinatumomab, nivolumab)ExperimentalPatients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate; Biological: Nivolumab
Group 4, Arm H (dexamethasone blinatumomab)ExperimentalPatients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with < 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.
Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Minimal residual disease (MRD) negative second remission (Rem-2) rate with blinatumomab vs with blinatumomab + nivolumab (Group 1)

    MRD negative Rem-2 be defined as Rem-2 (i.e., achievement of MRD < 1% blasts by flow cytometry and resolution of extramedullary disease (for CNS disease, requires CNS 1) ) and bone marrow with MRD < 0.01% by flow cytometry. MRD negative Rem-2 rate between Arm A vs Arm B will be compared using a one-sided Z test of proportions with Type I error of 0.10. Interim analysis will be conducted to monitor for futility. The futility boundaries are based on testing the alternative hypothesis at the 0.067 level.

    Measured: Up to 2 cycles of therapy (each cycle = 36 days)

  2. Event-free survival post-reinduction (EFS PR) (Group 3)

    Comparison of EFS post reinduction between Arm E versus Arm F will be based on a one-sided two-sample logrank test with Type I error of 0.15, to be conducted 3 years after completion of enrollment of Group 3. Interim analysis will be conducted to monitor for futility. The futility monitoring will be based on testing the alternative hypothesis at the 0.092 level. This alpha level corresponds to that which would cause futility stopping if the one-sided two-sample logrank test shows evidence of a hazard ratio > 1.0 when half of the expected events are observed.

    Measured: From date of randomization to date of treatment failure, relapse, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.

  3. EFS PR (Group 4)

    Comparison of EFS post reinduction between Arm H versus Arm I will be based on a one-sided two-sample logrank test with Type I error of 0.10, to be conducted 3 years after completion of enrollment of Group 3. Interim analysis will be conducted to monitor for futility. The futility monitoring will be based on testing the alternative hypothesis at the 0.092 level. This alpha level corresponds to that which would cause futility stopping if the one-sided two-sample logrank test shows evidence of a hazard ratio > 1.0 when half of the expected events are observed.

    Measured: From date of randomization to date of treatment failure, relapse, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.

Secondary outcomes (2)

  1. Dose-limiting toxicity

    Will be assessed using the Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 1 cycle of therapy (each cycle = 36 days)

  2. EFS PR (Group 4)

    Comparison of EFS post-reinduction between Arm C versus Arm D will be based on a one-sided two-sample logrank test with type I error of 0.15, to be conducted 2 years after completion of enrollment of Group 2. The futility monitoring will be based on testing the alternative hypothesis at the 0.092 level.

    Measured: From date of randomization to date of treatment failure, relapse, disease progression, SMN or death due to any cause, assessed up to 5 years after completion of enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2020
  2. Study start17 Dec 2020
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
461 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04546399
Sponsor's protocol ID
NCI-2020-06813
Other IDs
NCI-2020-06813, AALL1821, AALL1821, U10CA180886
Status last verified
Aug 2026
First submitted
11 Sep 2020
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Publications

  • Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

    PubMed 41671463

  • Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

    PubMed 35622074

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 3-Dimensional Conformal Radiation Therapy, Asparaginase Erwinia chrysanthemi and Biospecimen Collection in people with Down Syndrome and Recurrent B Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 227 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 227 sites in United States, Canada, Australia, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Minimal residual disease (MRD) negative second remission (Rem-2) rate with blinatumomab vs with blinatumomab + nivolumab (Group 1) (time frame: Up to 2 cycles of therapy (each cycle = 36 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04546399, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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