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

April 16, 2024 updated by: National Cancer Institute (NCI)

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 >/= 1 to < 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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

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 PI 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.

V. 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.

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 via infusion or IV 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: 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: 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: 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 2-3 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 1-15 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 1/2 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 1,15, 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 this cycle 1), MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2, and leucovorin calcium IV or PO q6h for 2 doses on days 2, 16 and 37 of cycle 1 and q6h for 2 doses on days 16 and 37 of cycle 2.

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.

Study Type

Interventional

Enrollment (Estimated)

550

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Hunter Regional Mail Centre, New South Wales, Australia, 2310
        • John Hunter Children's Hospital
      • Randwick, New South Wales, Australia, 2031
        • Sydney Children's Hospital
      • Westmead, New South Wales, Australia, 2145
        • The Children's Hospital at Westmead
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Queensland Children's Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Perth Children's Hospital
  • Canada
      • Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • The Montreal Children's Hospital of the MUHC
      • Montreal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
  • Puerto Rico
      • San Juan, Puerto Rico, 00926
        • University Pediatric Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
      • Mobile, Alabama, United States, 36604
        • USA Health Strada Patient Care Center
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Kingman, Arizona, United States, 86401
        • Kingman Regional Medical Center
      • Mesa, Arizona, United States, 85202
        • Banner Children's at Desert
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Arroyo Grande, California, United States, 93420
        • PCR Oncology
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Fontana, California, United States, 92335
        • Kaiser Permanente-Fontana
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90095
        • Mattel Children's Hospital UCLA
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Diego, California, United States, 92120
        • Kaiser Permanente-San Diego Zion
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • Torrance, California, United States, 90502
        • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Hospital
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61637
        • Saint Jude Midwest Affiliate
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Children's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Dearborn, Michigan, United States, 48124
        • Beaumont Hospital - Dearborn
      • East Lansing, Michigan, United States, 48824-7016
        • Michigan State University Clinical Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Trinity Health Grand Rapids Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49048
        • Borgess Medical Center
      • Muskegon, Michigan, United States, 49444
        • Trinity Health Muskegon Hospital
      • Niles, Michigan, United States, 49120
        • Lakeland Hospital Niles
      • Norton Shores, Michigan, United States, 49444
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Reed City, Michigan, United States, 49677
        • Spectrum Health Reed City Hospital
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
      • Royal Oak, Michigan, United States, 48073
        • Beaumont Children's Hospital-Royal Oak
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Medical Center Saint Joseph
      • Saint Joseph, Michigan, United States, 49085
        • Marie Yeager Cancer Center
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Troy, Michigan, United States, 48085
        • William Beaumont Hospital - Troy
      • Wyoming, Michigan, United States, 49519
        • Metro Health Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Carson Tahoe Regional Medical Center
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada - Henderson
      • Henderson, Nevada, United States, 89052
        • OptumCare Cancer Care at Seven Hills
      • Henderson, Nevada, United States, 89052
        • Las Vegas Cancer Center-Henderson
      • Henderson, Nevada, United States, 89074
        • Comprehensive Cancer Centers of Nevada-Southeast Henderson
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada-Horizon Ridge
      • Las Vegas, Nevada, United States, 89144
        • Summerlin Hospital Medical Center
      • Las Vegas, Nevada, United States, 89109
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, United States, 89102
        • OptumCare Cancer Care at Charleston
      • Las Vegas, Nevada, United States, 89128
        • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas, Nevada, United States, 89128
        • OptumCare Cancer Care at MountainView
      • Las Vegas, Nevada, United States, 89135
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89144
        • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas, Nevada, United States, 89144
        • Comprehensive Cancer Centers of Nevada-Summerlin
      • Las Vegas, Nevada, United States, 89148
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, United States, 89148
        • OptumCare Cancer Care at Fort Apache
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas, Nevada, United States, 89148-2405
        • Las Vegas Cancer Center-Medical Center
      • Las Vegas, Nevada, United States, 89128
        • Ann M Wierman MD LTD
      • Las Vegas, Nevada, United States, 89103
        • Hope Cancer Care of Nevada
      • Pahrump, Nevada, United States, 89048
        • Hope Cancer Care of Nevada-Pahrump
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
      • Reno, Nevada, United States, 89503
        • Saint Mary's Regional Medical Center
      • Reno, Nevada, United States, 89511
        • Cancer Care Specialists - Reno
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • Saint Joseph's Regional Medical Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Brooklyn, New York, United States, 11219
        • Maimonides Medical Center
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical Center of Akron
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • El Paso, Texas, United States, 79905
        • El Paso Children's Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78207
        • Children's Hospital of San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Vermont
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
    • Washington
      • Bellevue, Washington, United States, 98004
        • Overlake Medical Center
      • Renton, Washington, United States, 98055
        • Valley Medical Center
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Tacoma, Washington, United States, 98405
        • Mary Bridge Children's Hospital and Health Center
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
      • Yakima, Washington, United States, 98902
        • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • West Virginia
      • Bridgeport, West Virginia, United States, 26330
        • United Hospital Center
      • Martinsburg, West Virginia, United States, 25401
        • WVUH-Berkely Medical Center
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
      • Parkersburg, West Virginia, United States, 26101
        • Camden Clark Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

    • 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
    • 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 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)
  • 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 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. 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 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. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm G (dexamethasone, blinatumomab, nivolumab,MTX) 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 1,15, 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 this cycle 1), MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2, and leucovorin calcium IV or PO q6h for 2 doses on days 2, 16 and 37 of cycle 1 and q6h for 2 doses on days 16 and 37 of cycle 2.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Cytarabine
Given IT
Other Names:
  • .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
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Hydrocortisone Sodium Succinate
Given IT
Other Names:
  • (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
  • A-Hydrocort
  • Buccalsone
  • Corlan
  • Cortisol Sodium Succinate
  • Cortop
  • Efcortelan
  • Emergent-EZ
  • Flebocortid
  • Hidroc Clora
  • Hycorace
  • Hydro-Adreson
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: Leucovorin Calcium
Given PO and IV
Other Names:
  • Wellcovorin
  • folinic acid
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Experimental: Group 1, Arm A (dexamethasone, blinatumomab, MTX)
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.
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Cytarabine
Given IT
Other Names:
  • .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
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Hydrocortisone Sodium Succinate
Given IT
Other Names:
  • (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
  • A-Hydrocort
  • Buccalsone
  • Corlan
  • Cortisol Sodium Succinate
  • Cortop
  • Efcortelan
  • Emergent-EZ
  • Flebocortid
  • Hidroc Clora
  • Hycorace
  • Hydro-Adreson
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Experimental: Group 1, Arm B (dexamethasone, blinatumomab, MTX)
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.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Cytarabine
Given IT
Other Names:
  • .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
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Hydrocortisone Sodium Succinate
Given IT
Other Names:
  • (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
  • A-Hydrocort
  • Buccalsone
  • Corlan
  • Cortisol Sodium Succinate
  • Cortop
  • Efcortelan
  • Emergent-EZ
  • Flebocortid
  • Hidroc Clora
  • Hycorace
  • Hydro-Adreson
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Experimental: Group 2, Arm C (dexamethasone, blinatumomab, MTX)
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 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.
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Experimental: Group 2, Arm D (dexamethasone, nivolumab, blinatumomab, MTX)
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.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Experimental: Group 3, Arm E (dexamethasone, blinatumomab, MTX)
See Outline section
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Mercaptopurine
Given PO
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • U-4748
  • WR-2785
Drug: Pegaspargase
Given IM or IV
Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Thioguanine
Given PO
Other Names:
  • 6-TG
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
Drug: Cytarabine
Given IT
Other Names:
  • .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
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • 3D Conformal
  • Radiation, 3D Conformal
  • 3D radiotherapy
Drug: Hydrocortisone Sodium Succinate
Given IT
Other Names:
  • (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
  • A-Hydrocort
  • Buccalsone
  • Corlan
  • Cortisol Sodium Succinate
  • Cortop
  • Efcortelan
  • Emergent-EZ
  • Flebocortid
  • Hidroc Clora
  • Hycorace
  • Hydro-Adreson
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: Leucovorin Calcium
Given PO and IV
Other Names:
  • Wellcovorin
  • folinic acid
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Drug: Vincristine Sulfate
Given IV push or via infusion
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Experimental: Group 3, Arm F (dexamethasone, blinatumomab, nivolumab)
See Outline section
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Mercaptopurine
Given PO
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • U-4748
  • WR-2785
Drug: Pegaspargase
Given IM or IV
Other Names:
  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
Drug: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • Hemady
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
Biological: Blinatumomab
Given IV
Other Names:
  • Blincyto
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Thioguanine
Given PO
Other Names:
  • 6-TG
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
Drug: Cytarabine
Given IT
Other Names:
  • .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
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
  • 3D Conformal
  • Radiation, 3D Conformal
  • 3D radiotherapy
Drug: Hydrocortisone Sodium Succinate
Given IT
Other Names:
  • (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
  • A-Hydrocort
  • Buccalsone
  • Corlan
  • Cortisol Sodium Succinate
  • Cortop
  • Efcortelan
  • Emergent-EZ
  • Flebocortid
  • Hidroc Clora
  • Hycorace
  • Hydro-Adreson
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc
Drug: Leucovorin Calcium
Given PO and IV
Other Names:
  • Wellcovorin
  • folinic acid
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
Drug: Methotrexate
Given IT, PO, and IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Drug: Vincristine Sulfate
Given IV push or via infusion
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
Up to 2 cycles of therapy (each cycle = 36 days)
Event-free survival post-induction (Group 3)
Time Frame: From date of randomization to date of relapse, disease progression, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.
Comparison of EFS post induction between Arm E versus Arm F 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 0.067 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.
From date of randomization to date of relapse, disease progression, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicity
Time Frame: Up to 1 cycle of therapy (each cycle = 36 days)
Will be assessed using the Common Terminology Criteria for Adverse Events version 5.0.
Up to 1 cycle of therapy (each cycle = 36 days)
Event-free survival post-induction (Group 2)
Time Frame: 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
Comparison of EFS post-induction 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.
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (Group 1)
Time Frame: From date of Group 1 randomization to date of treatment failure, relapse, disease progression, SMN or death due to any cause, assessed up to 5 years
EFS will be compared between Arm A and Arm B, and to similar patients treated on AALL1331. These analyses will be performed using logrank tests, semi-parametric or parametric survival analysis methods, as appropriate.
From date of Group 1 randomization to date of treatment failure, relapse, disease progression, SMN or death due to any cause, assessed up to 5 years
Incidence of adverse events in Arm A or Arm B
Time Frame: Up to 1 cycle of therapy (each cycle = 36 days)
The toxicities as defined by grade 3 or greater reported adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab will be compared to similar patients treated with Block 1 of cytotoxic chemotherapy on AALL1331 using two-sample test of proportions.
Up to 1 cycle of therapy (each cycle = 36 days)
MRD negative Rem-2 rate (Group 2)
Time Frame: Up to 2 cycles of therapy (each cycle = 36 days)
MRD negative Rem-2 rate will be estimated and be compared between Arm C and Arm D using two-sample test of proportions.
Up to 2 cycles of therapy (each cycle = 36 days)
Dose-limiting toxicity (Down syndrome patients)
Time Frame: Up to 1 cycle of therapy (each cycle = 36 days)
Analyses will be largely descriptive.
Up to 1 cycle of therapy (each cycle = 36 days)
Incidence of adverse events (Down syndrome patients)
Time Frame: Up to 1 cycle of therapy (each cycle = 36 days)
Analyses will be largely descriptive.
Up to 1 cycle of therapy (each cycle = 36 days)
MRD negative Rem-2 rate (Down syndrome patients)
Time Frame: Up to 2 cycles of therapy (each cycle = 36 days)
Analyses will be largely descriptive.
Up to 2 cycles of therapy (each cycle = 36 days)
Subset analyses of EFS
Time Frame: Up to 2 cycles of therapy (each cycle = 36 days)
Features at first relapse 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, will be conducted. These analyses will be exploratory.
Up to 2 cycles of therapy (each cycle = 36 days)
Subset analyses of OS
Time Frame: Up to 2 cycles of therapy (each cycle = 36 days)
Features at first relapse 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, will be conducted. These analyses will be exploratory.
Up to 2 cycles of therapy (each cycle = 36 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Stacy L Cooper, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2020

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

September 11, 2020

First Submitted That Met QC Criteria

September 11, 2020

First Posted (Actual)

September 14, 2020

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-06813 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180886 (U.S. NIH Grant/Contract)
  • AALL1821 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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