Inotuzumab Ozogamicin and Blinatumomab in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia

April 23, 2024 updated by: National Cancer Institute (NCI)

A Phase II Study of Inotuzumab Ozogamicin Followed by Blinatumomab for Ph-Negative CD22-Positive B-Lineage Acute Lymphoblastic Leukemia in Newly Diagnosed Older Adults or Adults With Relapsed or Refractory Disease

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To confirm tolerability of the combination regimen of inotuzumab ozogamicin followed by blinatumomab.

II. To estimate the 1-year event-free survival of older, transplant-ineligible patients with newly diagnosed, Philadelphia (Ph)-negative, CD22-positive, B-cell acute lymphoblastic leukemia (ALL) treated with inotuzumab ozogamicin induction followed by blinatumomab consolidation. (Cohort 1) III. To estimate the 1-year event-free survival of patients with relapsed or refractory Ph-negative, CD22-positive, B-cell ALL treated with inotuzumab ozogamicin induction followed by blinatumomab consolidation. (Cohort 2)

SECONDARY OBJECTIVES:

I. To estimate the median, 1-year, and 3-year overall survival (OS) in all eligible patients. (Cohort 1) II. To estimate the median, 1-year, and 3-year relapse-free survival (RFS) in all eligible patients. (Cohort 1) III. To estimate the median and 3-year event-free survival (EFS) in all eligible patients. (Cohort 1) IV. To estimate the complete response (CR) rate and overall response rate (ORR, defined as complete response [CR] + complete response with incomplete count recovery [CRi]) to inotuzumab ozogamicin followed by blinatumomab (regimen CR rate and ORR). (Cohort 1) V. To estimate the CR rate and ORR (CR + CRi) to inotuzumab ozogamicin induction alone (induction CR and ORR). (Cohort 1) VI. To estimate the minimal residual disease (MRD) negativity rate in subjects achieving a CR or CRi. (Cohort 1) VII. To estimate the treatment-related mortality with this regimen. (Cohort 1) VIII. To describe the safety and tolerability of this regimen. (Cohort 1) IX. To estimate the median, 1-year, and 3-year OS in all eligible patients. (Cohort 2) X. To estimate the median, 1-year, and 3-year RFS in all eligible patients. (Cohort 2) XI. To estimate the median and 3-year EFS in all eligible patients. (Cohort 2) XII. To estimate ORR (CR/CRi and CR/complete response with partial hematologic recovery [CRh]) to blinatumomab in patients with ALL refractory to inotuzumab ozogamicin. (Cohort 2) XIII. To estimate the CR, CRi, and CRh rates at defined time points and cumulatively for the entire regimen. (Cohort 2) XIV. To determine the MRD negativity (< 10^-4) rate at defined time points including prior to allogeneic HCT and cumulatively in patients achieving a CR, CRh, or CRi. (Cohort 2) XV. To determine the allogeneic hematopoietic cell transplantation (HCT) rate in eligible subjects. (Cohort 2) XVI. To estimate the treatment-related mortality with this regimen. (Cohort 2) XVII. To describe the safety and tolerability of this regimen. (Cohort 2)

OTHER OBJECTIVES:

I. Results of the primary analysis will be examined for consistency, while accounting for the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

CORRELATIVE SCIENCE OBJECTIVES:

I. To correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters.

II. To correlate specific karyotype groups with response rates, response duration, survival, and cure in patients treated with inotuzumab ozogamicin followed by blinatumomab.

III. To correlate specific karyotype groups with MRD. IV. To determine karyotype changes at relapse and the influence of the type of change (or no change) in karyotype at relapse.

V. To assess the correlation of quantitative MRD post-induction with inotuzumab ozogamicin and at sequential consolidation time points with blinatumomab with RFS, EFS, and OS.

VI. To correlate the influence of MRD status (detectable versus [vs.] not and as a continuous measure) in relation to EFS, RFS, and OS with other clinical and biological factors (e.g. previously untreated vs. relapsed disease cohorts; age, initial white blood cell [WBC] count, cytogenetics).

VII. To identify genetic variants and predictors of ex vivo resistance. VIII. To identify genetic variants and predictors of MRD. IX. To identify genetic variants and predictors of relapse. X. To determine inter-patient variability in drug sensitivity of adult ALL. XI. To examine the associations of drug sensitivity with host and leukemia molecular features.

EXPLORATORY OBJECTIVES:

I. To estimate the median, 1-year, and 3-year RFS, EFS, and OS in patients achieving a CR/CRi to inotuzumab ozogamicin. (Cohort 1) II. To compare the median, 1-year, and 3-year RFS, EFS, and OS among patients achieving MRD-negative vs. MRD-positive CR/CRi to inotuzumab ozogamicin. (Cohort 1) III. To compare the median, 1-year, and 3-year RFS, EFS, and OS among patients achieving MRD-negative vs. MRD-positive CR/CRi at any time. (Cohort 1) IV. To describe the rate, severity, and timing of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver after limited inotuzumab ozogamicin exposure and identify risk factors for SOS/VOD. (Cohort 1) V. To estimate the rate of cytokine release syndrome in this population. (Cohort 1) VI. To estimate the median, 1-year, and 3-year RFS from time of CR/CRi to inotuzumab ozogamicin in patients receiving inotuzumab ozogamicin followed by blinatumomab and not undergoing allogeneic hematopoietic cell transplantation (HCT). (Cohort 2) VII. To estimate median, 1-year, and 3-year OS after CR/CRi to inotuzumab ozogamicin in patients not undergoing allogeneic HCT. (Cohort 2) VIII. To compare in a non-randomized fashion median, 1-year, and 3-year OS, median, 1-year, and 3-year RFS, cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) between patients achieving CR/CRi and receiving consolidation with or without allogeneic HCT. (Cohort 2) IX. To describe the rate, severity, and timing of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver after limited inotuzumab ozogamicin exposure and identify risk factors for SOS/VOD. (Cohort 2) X. To estimate the rate of cytokine release syndrome in this population. (Cohort 2)

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day 1, 8, and 15 (Course IA). By the end of Course IA (day 21), patients with adequate ALL cytoreduction continue to Course IB/IC, and patients who fail to achieve ALL cytoreduction continue to Course II. By the end of Course II, patients with CR-CRi to Course IB/IC and Course II continue to Course IIIA, patients without adequate ALL cytoreduction to Course IA or refractory to Course IB/IC but CR/CRi to Course II continue to Course IIIB.

COHORT 2: Patients receive inotuzumab ozogamicin IV over 1 hour on day 1, 8, and 15 (Course IA). By the end of Course IA (day 21), patients with adequate ALL cytoreduction continue to Course IB/IC, and patients who fail to achieve ALL cytoreduction continue to Course II. Patients with CR/CRi at the end of Course II continue to Course IIIB.

COURSE IB/IC: Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment continues for 1 course (28 days) in the absence of disease progression or unacceptable toxicity.

COURSE II: Patients receive blinatumomab IV continuously on days 1-28 and 43-70. Treatment continues for 1 course (84 days) in the absence of disease progression or unacceptable toxicity.

COURSE IIIA: Patients receive blinatumomab IV continuously on days 1-28 and 43-70. Treatment continues for 1 course (84 days) in the absence of disease progression or unacceptable toxicity.

COURSE IIIB: Patients receive blinatumomab IV continuously on days 1-28, 43-70, and 85-112. Treatment continues for 1 course (126 days) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years, and then every 6 months for up to 10 years.

Study Type

Interventional

Enrollment (Estimated)

64

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

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Active, not recruiting
        • University of Alabama at Birmingham Cancer Center
    • Alaska
      • Anchorage, Alaska, United States, 98508
        • Suspended
        • Anchorage Associates in Radiation Medicine
      • Anchorage, Alaska, United States, 99504
        • Suspended
        • Anchorage Radiation Therapy Center
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Breast Care and Surgery LLC
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Oncology and Hematology LLC
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Women's Cancer Care
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Anchorage Oncology Centre
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Katmai Oncology Group
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Providence Alaska Medical Center
    • Arizona
      • Kingman, Arizona, United States, 86401
        • Suspended
        • Kingman Regional Medical Center
    • Arkansas
      • Fort Smith, Arkansas, United States, 72903
        • Suspended
        • Mercy Hospital Fort Smith
    • California
      • Arroyo Grande, California, United States, 93420
        • Suspended
        • PCR Oncology
      • Burbank, California, United States, 91505
        • Suspended
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Clovis, California, United States, 93611
        • Recruiting
        • Community Cancer Institute
        • Principal Investigator:
          • Mohammed S. Bukari
        • Contact:
          • Site Public Contact
          • Phone Number: 559-387-1827
      • Clovis, California, United States, 93611
        • Suspended
        • University Oncology Associates
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Ibrahim Aldoss
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Principal Investigator:
          • James K. Mangan
        • Contact:
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
        • Principal Investigator:
          • Deepa Jeyakumar
        • Contact:
      • Palo Alto, California, United States, 94304
        • Active, not recruiting
        • Stanford Cancer Institute Palo Alto
    • Delaware
      • Frankford, Delaware, United States, 19945
        • Suspended
        • Beebe South Coastal Health Campus
      • Lewes, Delaware, United States, 19958
        • Suspended
        • Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Suspended
        • Delaware Clinical and Laboratory Physicians PA
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19718
        • Suspended
        • Christiana Care Health System-Christiana Hospital
      • Rehoboth Beach, Delaware, United States, 19971
        • Suspended
        • Beebe Health Campus
      • Seaford, Delaware, United States, 19973
        • Suspended
        • TidalHealth Nanticoke / Allen Cancer Center
      • Wilmington, Delaware, United States, 19801
        • Suspended
        • Christiana Care Health System-Wilmington Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Suspended
        • MedStar Georgetown University Hospital
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Suspended
        • Holy Cross Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Principal Investigator:
          • William G. Blum
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Principal Investigator:
          • William G. Blum
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
    • Idaho
      • Boise, Idaho, United States, 83712
        • Suspended
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, United States, 83619
        • Suspended
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Suspended
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83686
        • Suspended
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Suspended
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Alton, Illinois, United States, 62002
        • Suspended
        • Saint Anthony's Health
      • Bloomington, Illinois, United States, 61704
        • Suspended
        • Illinois CancerCare-Bloomington
      • Burr Ridge, Illinois, United States, 60527
        • Suspended
        • Loyola Center for Health at Burr Ridge
      • Canton, Illinois, United States, 61520
        • Suspended
        • Illinois CancerCare-Canton
      • Carbondale, Illinois, United States, 62902
        • Suspended
        • Memorial Hospital of Carbondale
      • Carterville, Illinois, United States, 62918
        • Suspended
        • SIH Cancer Institute
      • Carthage, Illinois, United States, 62321
        • Suspended
        • Illinois CancerCare-Carthage
      • Centralia, Illinois, United States, 62801
        • Suspended
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Principal Investigator:
          • Wendy Stock
        • Contact:
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Principal Investigator:
          • Shira N. Dinner
        • Contact:
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois
        • Contact:
          • Site Public Contact
          • Phone Number: 312-355-3046
        • Principal Investigator:
          • John G. Quigley
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Suspended
        • Decatur Memorial Hospital
      • Dixon, Illinois, United States, 61021
        • Suspended
        • Illinois CancerCare-Dixon
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Eureka, Illinois, United States, 61530
        • Suspended
        • Illinois CancerCare-Eureka
      • Galesburg, Illinois, United States, 61401
        • Suspended
        • Western Illinois Cancer Treatment Center
      • Galesburg, Illinois, United States, 61401
        • Suspended
        • Illinois CancerCare-Galesburg
      • Homer Glen, Illinois, United States, 60491
        • Suspended
        • Loyola Medicine Homer Glen
      • Kewanee, Illinois, United States, 61443
        • Suspended
        • Illinois CancerCare-Kewanee Clinic
      • Lake Forest, Illinois, United States, 60045
        • Active, not recruiting
        • Northwestern Medicine Lake Forest Hospital
      • Macomb, Illinois, United States, 61455
        • Suspended
        • Illinois CancerCare-Macomb
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center
        • Principal Investigator:
          • Stephanie B. Tsai
        • Contact:
          • Site Public Contact
          • Phone Number: 708-226-4357
      • Melrose Park, Illinois, United States, 60160
        • Suspended
        • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
      • Mount Vernon, Illinois, United States, 62864
        • Suspended
        • Good Samaritan Regional Health Center
      • New Lenox, Illinois, United States, 60451
        • Recruiting
        • UC Comprehensive Cancer Center at Silver Cross
        • Principal Investigator:
          • Wendy Stock
        • Contact:
      • O'Fallon, Illinois, United States, 62269
        • Suspended
        • Cancer Care Center of O'Fallon
      • Orland Park, Illinois, United States, 60462
        • Recruiting
        • University of Chicago Medicine-Orland Park
        • Principal Investigator:
          • Wendy Stock
        • Contact:
      • Ottawa, Illinois, United States, 61350
        • Suspended
        • Illinois CancerCare-Ottawa Clinic
      • Pekin, Illinois, United States, 61554
        • Suspended
        • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
      • Pekin, Illinois, United States, 61554
        • Suspended
        • Illinois CancerCare-Pekin
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois CancerCare-Peoria
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peoria, Illinois, United States, 61636
        • Suspended
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61615
        • Suspended
        • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
      • Peoria, Illinois, United States, 61637
        • Suspended
        • OSF Saint Francis Medical Center
      • Peru, Illinois, United States, 61354
        • Suspended
        • Valley Radiation Oncology
      • Peru, Illinois, United States, 61354
        • Suspended
        • Illinois CancerCare-Peru
      • Princeton, Illinois, United States, 61356
        • Suspended
        • Illinois CancerCare-Princeton
      • Springfield, Illinois, United States, 62781
        • Suspended
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Suspended
        • Springfield Clinic
      • Springfield, Illinois, United States, 62702
        • Suspended
        • Southern Illinois University School of Medicine
      • Washington, Illinois, United States, 61571
        • Suspended
        • Illinois CancerCare - Washington
    • Kansas
      • Garden City, Kansas, United States, 67846
        • Suspended
        • Central Care Cancer Center - Garden City
      • Great Bend, Kansas, United States, 67530
        • Suspended
        • Central Care Cancer Center - Great Bend
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Principal Investigator:
          • Kenneth Byrd
        • Contact:
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Principal Investigator:
          • Kenneth Byrd
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Active, not recruiting
        • Ochsner Medical Center Jefferson
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Active, not recruiting
        • University of Maryland/Greenebaum Cancer Center
    • Massachusetts
      • Springfield, Massachusetts, United States, 01104
        • Suspended
        • Mercy Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Brighton, Michigan, United States, 48114
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Christopher M. Reynolds
      • Canton, Michigan, United States, 48188
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Christopher M. Reynolds
      • Caro, Michigan, United States, 48723
        • Suspended
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Christopher M. Reynolds
      • Clarkston, Michigan, United States, 48346
        • Suspended
        • Hematology Oncology Consultants-Clarkston
      • Clarkston, Michigan, United States, 48346
        • Suspended
        • Newland Medical Associates-Clarkston
      • Detroit, Michigan, United States, 48236
        • Recruiting
        • Ascension Saint John Hospital
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • East China Township, Michigan, United States, 48054
        • Recruiting
        • Great Lakes Cancer Management Specialists-Doctors Park
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Cancer and Blood Disease Treatment Center
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Flint, Michigan, United States, 48503
        • Suspended
        • Hurley Medical Center
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Recruiting
        • Academic Hematology Oncology Specialists
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Recruiting
        • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Suspended
        • Michigan Breast Specialists-Grosse Pointe Woods
      • Lansing, Michigan, United States, 48912
        • Suspended
        • University of Michigan Health - Sparrow Lansing
      • Livonia, Michigan, United States, 48154
        • Suspended
        • Hope Cancer Clinic
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Christopher M. Reynolds
      • Macomb, Michigan, United States, 48044
        • Recruiting
        • Great Lakes Cancer Management Specialists-Macomb Medical Campus
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Macomb, Michigan, United States, 48044
        • Suspended
        • Michigan Breast Specialists-Macomb Township
      • Marlette, Michigan, United States, 48453
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Pontiac, Michigan, United States, 48341
        • Suspended
        • 21st Century Oncology-Pontiac
      • Pontiac, Michigan, United States, 48341
        • Suspended
        • Hope Cancer Center
      • Pontiac, Michigan, United States, 48341
        • Suspended
        • Newland Medical Associates-Pontiac
      • Pontiac, Michigan, United States, 48341
        • Suspended
        • Saint Joseph Mercy Oakland
      • Rochester Hills, Michigan, United States, 48309
        • Suspended
        • Great Lakes Cancer Management Specialists-Rochester Hills
      • Saginaw, Michigan, United States, 48601
        • Suspended
        • Ascension Saint Mary's Hospital
      • Saginaw, Michigan, United States, 48604
        • Suspended
        • Oncology Hematology Associates of Saginaw Valley PC
      • Sterling Heights, Michigan, United States, 48312
        • Recruiting
        • Bhadresh Nayak MD PC-Sterling Heights
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Tawas City, Michigan, United States, 48764
        • Suspended
        • Ascension Saint Joseph Hospital
      • Warren, Michigan, United States, 48093
        • Recruiting
        • Great Lakes Cancer Management Specialists-Macomb Professional Building
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Warren, Michigan, United States, 48093
        • Recruiting
        • Macomb Hematology Oncology PC
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Warren, Michigan, United States, 48093
        • Recruiting
        • Saint John Macomb-Oakland Hospital
        • Principal Investigator:
          • Christopher M. Reynolds
        • Contact:
      • Warren, Michigan, United States, 48088
        • Suspended
        • Advanced Breast Care Center PLLC
      • Warren, Michigan, United States, 48093
        • Suspended
        • Michigan Breast Specialists-Warren
      • West Branch, Michigan, United States, 48661
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Christopher M. Reynolds
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Mayo Clinic in Rochester
    • Missouri
      • Ballwin, Missouri, United States, 63011
        • Suspended
        • Saint Louis Cancer and Breast Institute-Ballwin
      • Bolivar, Missouri, United States, 65613
        • Suspended
        • Central Care Cancer Center - Bolivar
      • Branson, Missouri, United States, 65616
        • Suspended
        • Cox Cancer Center Branson
      • Cape Girardeau, Missouri, United States, 63703
        • Suspended
        • Southeast Cancer Center
      • Cape Girardeau, Missouri, United States, 63703
        • Suspended
        • Saint Francis Medical Center
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Principal Investigator:
          • Geoffrey L. Uy
        • Contact:
      • Farmington, Missouri, United States, 63640
        • Suspended
        • Parkland Health Center - Farmington
      • Jefferson City, Missouri, United States, 65109
        • Suspended
        • Capital Region Southwest Campus
      • Joplin, Missouri, United States, 64804
        • Suspended
        • Freeman Health System
      • Joplin, Missouri, United States, 64804
        • Suspended
        • Mercy Hospital Joplin
      • Rolla, Missouri, United States, 65401
        • Suspended
        • Delbert Day Cancer Institute at PCRMC
      • Rolla, Missouri, United States, 65401
        • Suspended
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Joseph, Missouri, United States, 64506
        • Suspended
        • Heartland Regional Medical Center
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Geoffrey L. Uy
        • Contact:
      • Saint Louis, Missouri, United States, 63109
        • Suspended
        • Saint Louis Cancer and Breast Institute-South City
      • Saint Louis, Missouri, United States, 63128
        • Suspended
        • Mercy Hospital South
      • Saint Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Principal Investigator:
          • Geoffrey L. Uy
        • Contact:
      • Saint Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Principal Investigator:
          • Geoffrey L. Uy
        • Contact:
      • Saint Louis, Missouri, United States, 63141
        • Suspended
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63131
        • Suspended
        • Missouri Baptist Medical Center
      • Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Principal Investigator:
          • Geoffrey L. Uy
        • Contact:
      • Sainte Genevieve, Missouri, United States, 63670
        • Suspended
        • Sainte Genevieve County Memorial Hospital
      • Springfield, Missouri, United States, 65804
        • Suspended
        • Mercy Hospital Springfield
      • Springfield, Missouri, United States, 65807
        • Suspended
        • CoxHealth South Hospital
      • Sullivan, Missouri, United States, 63080
        • Suspended
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • Suspended
        • BJC Outpatient Center at Sunset Hills
      • Washington, Missouri, United States, 63090
        • Suspended
        • Mercy Hospital Washington
    • Montana
      • Missoula, Montana, United States, 59802
        • Suspended
        • Saint Patrick Hospital - Community Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Active, not recruiting
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68118
        • Active, not recruiting
        • Nebraska Medicine-Village Pointe
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Suspended
        • Carson Tahoe Regional Medical Center
      • Henderson, Nevada, United States, 89052
        • Suspended
        • Cancer and Blood Specialists-Henderson
      • Henderson, Nevada, United States, 89052
        • Suspended
        • Comprehensive Cancer Centers of Nevada - Henderson
      • Henderson, Nevada, United States, 89052
        • Suspended
        • Comprehensive Cancer Centers of Nevada-Horizon Ridge
      • Henderson, Nevada, United States, 89052
        • Suspended
        • Las Vegas Cancer Center-Henderson
      • Henderson, Nevada, United States, 89052
        • Suspended
        • OptumCare Cancer Care at Seven Hills
      • Henderson, Nevada, United States, 89074
        • Suspended
        • Comprehensive Cancer Centers of Nevada-Southeast Henderson
      • Henderson, Nevada, United States, 89074
        • Suspended
        • GenesisCare USA - Henderson
      • Henderson, Nevada, United States, 89074
        • Suspended
        • Las Vegas Urology - Green Valley
      • Henderson, Nevada, United States, 89074
        • Suspended
        • Las Vegas Urology - Pebble
      • Henderson, Nevada, United States, 89074
        • Suspended
        • Urology Specialists of Nevada - Green Valley
      • Las Vegas, Nevada, United States, 89102
        • Suspended
        • Desert West Surgery
      • Las Vegas, Nevada, United States, 89102
        • Recruiting
        • OptumCare Cancer Care at Charleston
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
      • Las Vegas, Nevada, United States, 89109
        • Suspended
        • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
      • Las Vegas, Nevada, United States, 89113
        • Suspended
        • HealthCare Partners Medical Group Oncology/Hematology-San Martin
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
      • Las Vegas, Nevada, United States, 89148
        • Recruiting
        • OptumCare Cancer Care at Fort Apache
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
      • Las Vegas, Nevada, United States, 89149
        • Suspended
        • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
      • Las Vegas, Nevada, United States, 89074
        • Suspended
        • Las Vegas Urology - Pecos
      • Las Vegas, Nevada, United States, 89102
        • Suspended
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, United States, 89103
        • Suspended
        • Hope Cancer Care of Nevada
      • Las Vegas, Nevada, United States, 89106
        • Suspended
        • Radiation Oncology Centers of Nevada Central
      • Las Vegas, Nevada, United States, 89106
        • Suspended
        • Urology Specialists of Nevada - Central
      • Las Vegas, Nevada, United States, 89109
        • Suspended
        • GenesisCare USA - Las Vegas
      • Las Vegas, Nevada, United States, 89109
        • Suspended
        • Sunrise Hospital and Medical Center
      • Las Vegas, Nevada, United States, 89113
        • Suspended
        • Las Vegas Prostate Cancer Center
      • Las Vegas, Nevada, United States, 89113
        • Suspended
        • Las Vegas Urology - Sunset
      • Las Vegas, Nevada, United States, 89113
        • Suspended
        • Urology Specialists of Nevada - Southwest
      • Las Vegas, Nevada, United States, 89119
        • Suspended
        • Radiation Oncology Centers of Nevada Southeast
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • Ann M Wierman MD LTD
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • GenesisCare USA - Vegas Tenaya
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • Las Vegas Urology - Cathedral Rock
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • Las Vegas Urology - Smoke Ranch
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • OptumCare Cancer Care at MountainView
      • Las Vegas, Nevada, United States, 89128
        • Suspended
        • Urology Specialists of Nevada - Northwest
      • Las Vegas, Nevada, United States, 89135
        • Suspended
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas, Nevada, United States, 89144
        • Suspended
        • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas, Nevada, United States, 89144
        • Suspended
        • Comprehensive Cancer Centers of Nevada-Summerlin
      • Las Vegas, Nevada, United States, 89144
        • Suspended
        • Summerlin Hospital Medical Center
      • Las Vegas, Nevada, United States, 89148-2405
        • Suspended
        • Las Vegas Cancer Center-Medical Center
      • Las Vegas, Nevada, United States, 89148
        • Suspended
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, United States, 89148
        • Suspended
        • GenesisCare USA - Fort Apache
      • Las Vegas, Nevada, United States, 89169
        • Suspended
        • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas, Nevada, United States, 89169
        • Suspended
        • University Cancer Center
      • Pahrump, Nevada, United States, 89048
        • Suspended
        • Hope Cancer Care of Nevada-Pahrump
      • Reno, Nevada, United States, 89502
        • Suspended
        • Renown Regional Medical Center
      • Reno, Nevada, United States, 89503
        • Suspended
        • Saint Mary's Regional Medical Center
      • Reno, Nevada, United States, 89509
        • Suspended
        • Radiation Oncology Associates
    • New York
      • Buffalo, New York, United States, 14263
        • Active, not recruiting
        • Roswell Park Cancer Institute
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health/Center for Advanced Medicine
        • Contact:
          • Site Public Contact
          • Phone Number: 516-734-8896
        • Principal Investigator:
          • Bradley H. Goldberg
      • Manhasset, New York, United States, 11030
        • Recruiting
        • North Shore University Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 516-734-8896
        • Principal Investigator:
          • Bradley H. Goldberg
      • New Hyde Park, New York, United States, 11040
        • Recruiting
        • Long Island Jewish Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 516-734-8896
        • Principal Investigator:
          • Bradley H. Goldberg
      • New York, New York, United States, 10065
        • Suspended
        • NYP/Weill Cornell Medical Center
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
        • Principal Investigator:
          • Paul M. Barr
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Suspended
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Active, not recruiting
        • Duke University Medical Center
      • Greenville, North Carolina, United States, 27834
        • Suspended
        • East Carolina University
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Bayard L. Powell
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Emily K. Curran
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Principal Investigator:
          • Gregory K. Behbehani
        • Contact:
      • West Chester, Ohio, United States, 45069
        • Recruiting
        • University of Cincinnati Cancer Center-West Chester
        • Principal Investigator:
          • Emily K. Curran
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Principal Investigator:
          • Adam S. Asch
        • Contact:
      • Oklahoma City, Oklahoma, United States, 73120
        • Suspended
        • Mercy Hospital Oklahoma City
    • Oregon
      • Bend, Oregon, United States, 97701
        • Suspended
        • Saint Charles Health System
      • Clackamas, Oregon, United States, 97015
        • Recruiting
        • Providence Cancer Institute Clackamas Clinic
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Clackamas, Oregon, United States, 97015
        • Recruiting
        • Clackamas Radiation Oncology Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Coos Bay, Oregon, United States, 97420
        • Suspended
        • Bay Area Hospital
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97239
        • Active, not recruiting
        • Oregon Health and Science University
      • Redmond, Oregon, United States, 97756
        • Suspended
        • Saint Charles Health System-Redmond
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Suspended
        • Lehigh Valley Hospital-Cedar Crest
      • Bethlehem, Pennsylvania, United States, 18017
        • Suspended
        • Lehigh Valley Hospital - Muhlenberg
      • Chadds Ford, Pennsylvania, United States, 19317
        • Suspended
        • Christiana Care Health System-Concord Health Center
      • East Stroudsburg, Pennsylvania, United States, 18301
        • Suspended
        • Pocono Medical Center
      • Hazleton, Pennsylvania, United States, 18201
        • Suspended
        • Lehigh Valley Hospital-Hazleton
      • Philadelphia, Pennsylvania, United States, 19107
        • Active, not recruiting
        • Thomas Jefferson University Hospital
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Principal Investigator:
          • Keri R. Maher
        • Contact:
    • Washington
      • Aberdeen, Washington, United States, 98520
        • Suspended
        • Providence Regional Cancer System-Aberdeen
      • Bellevue, Washington, United States, 98004
        • Suspended
        • Overlake Medical Center
      • Bellingham, Washington, United States, 98225
        • Suspended
        • PeaceHealth Saint Joseph Medical Center
      • Centralia, Washington, United States, 98531
        • Suspended
        • Providence Regional Cancer System-Centralia
      • Edmonds, Washington, United States, 98026
        • Suspended
        • Swedish Cancer Institute-Edmonds
      • Everett, Washington, United States, 98201
        • Suspended
        • Providence Regional Cancer Partnership
      • Issaquah, Washington, United States, 98029
        • Suspended
        • Swedish Cancer Institute-Issaquah
      • Kennewick, Washington, United States, 99336
        • Suspended
        • Kadlec Clinic Hematology and Oncology
      • Lacey, Washington, United States, 98503
        • Suspended
        • Providence Regional Cancer System-Lacey
      • Longview, Washington, United States, 98632
        • Suspended
        • PeaceHealth Saint John Medical Center
      • Renton, Washington, United States, 98055
        • Suspended
        • Valley Medical Center
      • Seattle, Washington, United States, 98104
        • Suspended
        • Pacific Gynecology Specialists
      • Seattle, Washington, United States, 98107
        • Suspended
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122-5711
        • Suspended
        • Swedish Medical Center-Cherry Hill
      • Seattle, Washington, United States, 98122
        • Suspended
        • Swedish Medical Center-First Hill
      • Sedro-Woolley, Washington, United States, 98284
        • Suspended
        • PeaceHealth United General Medical Center
      • Shelton, Washington, United States, 98584
        • Suspended
        • Providence Regional Cancer System-Shelton
      • Vancouver, Washington, United States, 98664
        • Suspended
        • PeaceHealth Southwest Medical Center
      • Walla Walla, Washington, United States, 99362
        • Suspended
        • Providence Saint Mary Regional Cancer Center
      • Yakima, Washington, United States, 98902
        • Suspended
        • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
      • Yelm, Washington, United States, 98597
        • Suspended
        • Providence Regional Cancer System-Yelm
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Suspended
        • West Virginia University Healthcare
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Principal Investigator:
          • Ryan J. Mattison
        • Contact:
      • Marshfield, Wisconsin, United States, 54449
      • Milwaukee, Wisconsin, United States, 53226
        • Suspended
        • Medical College of Wisconsin
      • Minocqua, Wisconsin, United States, 54548
      • Rice Lake, Wisconsin, United States, 54868
      • Stevens Point, Wisconsin, United States, 54482
      • Weston, Wisconsin, United States, 54476

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pre-registration Eligibility Criteria (Step 0)

  • Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration. The specimens should be sent to the HEME Biobank.

    • Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:

      • Patients may receive the day 1 of course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then systemic chemotherapy must begin within 7 days of this IT chemotherapy.
  • Registration Eligibility Criteria (Step 1)
  • Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are not eligible.
  • CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local hematopathology evaluation.
  • Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, fluorescence in situ hybridization (FISH), and/or polymerase chain reaction (PCR). If any test is positive for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.

  • No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed). Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurological dysfunction) within the 28 days prior to registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for additional guidance. Prophylactic intrathecal medication alone is not an exclusion.

    • Categories of CNS Involvement for CNS Evaluation Prior to Registration:

      • CNS 1: CSF has < 5 WBC/uL with cytospin negative for blasts; or >= 10 red blood cell (RBC)/uL with cytospin negative for blasts.
      • CNS 2: CSF has < 5 WBC/uL with cytospin positive for blasts; or >= 10 RBC/uL with cytospin positive for blasts; or >= 10 RBC/uL, WBC/uL >= 5 but less than Steinherz/Bleyer algorithm with cytospin positive for blasts (see below).

      • CNS 3: CSF has >= 5 WBC/uL with cytospin positive for blasts; or >= 10 RBC/uL, >= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below); or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating Initial Traumatic Lumbar Punctures:

        • If the patient has leukemia cells in the peripheral blood and the lumbar puncture is traumatic and contains >= 5 WBC/uL with blasts, the following algorithm should be used to define CNS disease: CSF WBC/CSF RBC > 2 x (Blood WBC/Blood RBC count)

  • Patients with known or suspected testicular involvement by leukemia are allowed provided that the patient receives concomitant scrotal/testicular radiotherapy.

    • Unilateral or bilateral testicular enlargement should be assessed by ultrasound or other imaging technique. Biopsy is recommended if clinical findings are equivocal or suggestive of hydrocele or a non-leukemic mass, but further assessments are per treating physician discretion.

  • Not pregnant and not nursing.

    • This study involves agents that have known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required.
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • No unstable cardiac disease such as myocardial infarction, angina pectoris, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of registration.
  • No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) < 45% or New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF).
  • Patients with known human immunodeficiency virus (HIV) infection are eligible if they have been on effective antiretroviral therapy with an undetectable viral load tested within 6 months of registration.

  • Patients with hepatitis B virus (HBV) are eligible only if they meet all the following:

    • On HBV-suppressive therapy.
    • No evidence of active virus.
    • No evidence of HBV-related liver damage.

  • Patients with hepatitis C virus (HCV) are eligible only if they meet all the following:

    • Successfully completed complete-eradication therapy with undetectable viral load.
    • No evidence of HCV-related liver damage.
  • No history of clinically relevant neurologic disorder such as epilepsy, seizure, aphasia, stroke, severe brain injury, structural brain abnormality, benign brain tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other significant CNS abnormalities.
  • No prior additional malignancy (i.e. in addition to ALL) except adequately treated basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for >= 2 years.
  • No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal syncope, or chronic bradycardic states such as sinoatrial block or higher degree of atrioventricular block unless a permanent pacemaker has been implanted.
  • No history of chronic liver disease, including cirrhosis.
  • No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
  • No uncontrolled infection or recent history (within 4 months prior to registration) of deep tissue infections such as fasciitis or osteomyelitis.

  • Total bilirubin, serum =< 1.5 x upper limit of normal (ULN)*

    • Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =< 2 x ULN.
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine, serum =< 1.5 ULN OR creatinine clearance >= 40 mL/min
  • QT interval by Fridericia's correction formula (QTcF) =< 470 msec
  • Cohort 1 Patients Only
  • Age >= 60 years.
  • No prior treatment for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed therapy may be administered for no more than 14 days and must be completed >= 24 hours prior to the initiation of protocol therapy.
  • No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
  • Cohort 2 Patients Only:
  • Age >= 18 years.
  • Relapsed or refractory disease in salvage 1 or 2.
  • No isolated extramedullary relapse.
  • Prior allogeneic HCT permitted.
  • Patients with prior allogeneic HCT must have completed transplantation >= 4 months prior to registration.
  • Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease and must have completed immunosuppressive therapy >= 30 days prior to registration.
  • Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy, or other CD19-directed therapy is not allowed.
  • Prior treatment with rituximab must be completed >= 7 days prior to registration.
  • Prior treatment with other monoclonal antibodies must be completed >= 6 weeks prior to registration.
  • Prior treatment for ALL must be completed >= 14 days prior to registration with the following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids, 6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce circulating absolute lymphoblast count to =< 10,000/uL or prevent complications related to ALL are allowed but must be completed >= 24 hours prior to the initiation of protocol therapy.
  • Patients should have resolution of any acute non-hematologic toxicities of prior therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 grade =< 1.
  • Peripheral blood absolute lymphoblast count =< 10,000/uL (treatment allowed as above to reduce blast count to =< 10,000/uL)

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (inotuzumab ozogamicin, blinatumomab)
See Detailed Description
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
  • AMG 103
  • MT103
  • MEDI538
Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294
Experimental: Cohort 2 (inotuzumab ozogamicin, blinatumomab)
See Detailed Description.
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
  • AMG 103
  • MT103
  • MEDI538
Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: At 1 year
Will be defined as time from start of treatment to failure to achieve complete response (CR)/complete response with incomplete count recovery (CRi) after completing Course II of blinatumomab, relapse after CR/CRi, progression on study requiring withdrawal from study therapy, or death from any cause
At 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Time from start of study therapy to death from any cause censored at the last known alive date, assessed up to 10 years
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Time from start of study therapy to death from any cause censored at the last known alive date, assessed up to 10 years
Relapse-free survival (RFS)
Time Frame: Time from first CR/CRi to progressive disease (relapse, treatment discontinuation due to health deterioration) or death, assessed up to 10 years
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Time from first CR/CRi to progressive disease (relapse, treatment discontinuation due to health deterioration) or death, assessed up to 10 years
Event-free survival (EFS)
Time Frame: Time from start of treatment to failure to achieve CR/CRi after completing Course II of blinatumomab, relapse after CR/CRi, progression on study requiring withdrawal from study therapy, or death from any cause, assessed up to 10 years
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Time from start of treatment to failure to achieve CR/CRi after completing Course II of blinatumomab, relapse after CR/CRi, progression on study requiring withdrawal from study therapy, or death from any cause, assessed up to 10 years
Complete and overall response rate
Time Frame: Up to 10 years
Point and interval estimates of the rates will be shown using a 95% binomial confidence interval.
Up to 10 years
Minimal residual disease negativity
Time Frame: Up to 10 years
Up to 10 years
Allogeneic hematopoietic cell transplantation rate (Cohort 2)
Time Frame: Up to 10 years
Point and interval estimates of the rate will be shown using a 95% binomial confidence interval.
Up to 10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of cytokine release syndrome (Cohort 1)
Time Frame: Up to 10 years
Point and interval estimates of the rate will be shown using a 95% binomial confidence interval.
Up to 10 years
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver
Time Frame: Up to 10 years
The rate of, timing of, and risk factors for SOS/VOD of the liver after limited inotuzumab ozogamicin exposure. Point and interval estimates of the rate will be shown using a 95% binomial confidence interval. A summary of the timing and risk factors for SOS/VOD of the liver will be provided.
Up to 10 years
OS
Time Frame: Up to 2 years
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation versus (vs.) patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. The median, 1-year, and 2-year OS will be compared between the above two groups. The distribution of OS for each group will be estimated using the Kaplan-Meier method.
Up to 2 years
RFS
Time Frame: Up to 2 years
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation vs. patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. The median, 1-year, and 2-year RFS will be compared between the above two groups. The distribution of RFS for each treatment arm will be estimated using the Kaplan-Meier method.
Up to 2 years
Cumulative incidence of relapse (CIR)
Time Frame: Up to 2 years
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation vs. patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. Competing risk analysis will be done to compare the relapse rates between the above two groups. In this analysis, death will be considered a competing event. Relapse rates at the 1-year and 2-year time points will be estimated. Other time points of interest may be estimated as well.
Up to 2 years
Non-relapse mortality
Time Frame: Up to 2 years
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation vs. patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. Competing risk analysis will be done to compare the mortality rates between the above two groups. In this analysis, relapse will be considered a competing event. Mortality rates at the 1-year and 2-year time points will be estimated. Other time points may be estimated as well.
Up to 2 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Matthew J Wieduwilt, Alliance for Clinical Trials in Oncology

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)

May 8, 2019

Primary Completion (Estimated)

February 1, 2025

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

November 12, 2018

First Submitted That Met QC Criteria

November 12, 2018

First Posted (Actual)

November 14, 2018

Study Record Updates

Last Update Posted (Actual)

April 24, 2024

Last Update Submitted That Met QC Criteria

April 23, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2018-02484 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • A041703 (Other Identifier: CTEP)

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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