Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)
3 other identifiers
interventional
80
2 countries
157
Brief Summary
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2017
Longer than P75 for phase_2
157 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 29, 2016
CompletedFirst Posted
Study publicly available on registry
December 5, 2016
CompletedStudy Start
First participant enrolled
June 19, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
May 4, 2026
April 1, 2026
9.5 years
November 29, 2016
April 28, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Morphologic response (complete response [CR]+ incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin (Cohort 1)
The response rate will be estimated using the proportion of eligible/evaluable patients with CR/CRi response. A one-sided lower 95% Agresti-Coull confidence limit will be calculated.
Up to 28 days
Secondary Outcomes (10)
Morphologic response (CR + CRi) following 2 cycles of inotuzumab ozogamicin therapy (Cohort1)
Up to 56 days
Incidence of dose-limiting toxicities at recommended phase II dose (RP2D) (Cohort 1)
During Cycle 1, up to 28 days
Level of minimal residual disease (MRD) assessed in bone marrow by flow cytometry (Cohort 1 and 2)
Up to 2 cycles
Incidence of adverse events of sinusoidal obstruction syndrome (SOS) of liver (Cohort 1 and 2)
Up to 1 year from last dose of Inotuzumab ozogamicin
Event free survival (EFS) (Cohort 1)
From study entry to first event (induction failure, induction death, relapse, second malignancy, remission death), or date of last follow-up for event free subjects, assessed up to 3 years
- +5 more secondary outcomes
Other Outcomes (10)
Changes in CD22 surface expression (Cohorts 1 and 2)
Baseline, post Cycle 1, and at time of relapse
Change in CD22 site density (Cohorts 1 and 2)
Baseline, post Cycle 1, and at time of relapse
Leukemic blast CD22 splice variants (Cohorts 1 and 2)
Baseline, post-Cycle 1, and at time of relapse
- +7 more other outcomes
Study Arms (2)
Cohort I (inotuzumab ozogamicin)
EXPERIMENTALPatients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. (COMPLETE)
Cohort II (inotuzumab ozogamicin, mBFM chemotherapy)
EXPERIMENTALSee Detailed Description
Interventions
Given IV
Given IV or SC
Undergo imaging
Given IV
Given PO or IV
Undergo lumbar puncture
Given IT
Given IV or IM
Given IV
Undergo blood sample collection
Undergo a bone marrow aspiration and biopsy
Given IV
Given Asparaginase Erwinia chrysanthemi
Eligibility Criteria
You may qualify if:
- Patients must be \>= 1 year and \< 22 years of age at the time of enrollment
- Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with \>= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
- NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
- Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing \>= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
- Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin \[PE\] is strongly recommended)
- In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
- Patients with one of the following:
- Second or greater relapse;
- Primary refractory disease with at least 2 prior induction attempts;
- First relapse refractory to at least one prior re-induction attempt
- Any relapse after HSCT (Cohort 1 ONLY)
- Patients with Down syndrome are eligible ONLY for Cohort 1 with:
- Any of above disease status, OR
- First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
- Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
You may not qualify if:
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
- A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
- A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
- \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, \>= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
- Note: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy.
- Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
- Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
- Radiotherapy: \>= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); \>= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if \>= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; \>= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
- Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
- Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or
- A serum creatinine based on age/sex as follows:
- to \< 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
- to \< 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (157)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Tampa General Hospital
Tampa, Florida, 33606, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Medical Center
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260, United States
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
Maine Children's Cancer Program
Scarborough, Maine, 04074, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Tufts Children's Hospital
Boston, Massachusetts, 02111, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Michigan State University
East Lansing, Michigan, 48823, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Corewell Health Children's
Royal Oak, Michigan, 48073, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
University of Missouri Children's Hospital
Columbia, Missouri, 65212, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144, United States
Renown Regional Medical Center
Reno, Nevada, 89502, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Albany Medical Center
Albany, New York, 12208, United States
Maimonides Medical Center
Brooklyn, New York, 11219, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
New York Medical College
Valhalla, New York, 10595, United States
Mission Hospital
Asheville, North Carolina, 28801, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Covenant Children's Hospital
Lubbock, Texas, 79410, United States
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415, United States
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
HIMA San Pablo Oncologic Hospital
Caguas, 00726, Puerto Rico
Related Publications (2)
Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
PMID: 35622074DERIVEDO'Brien MM, Ji L, Shah NN, Rheingold SR, Bhojwani D, Yuan CM, Xu X, Yi JS, Harris AC, Brown PA, Borowitz MJ, Militano O, Kairalla J, Devidas M, Raetz EA, Gore L, Loh ML. Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621. J Clin Oncol. 2022 Mar 20;40(9):956-967. doi: 10.1200/JCO.21.01693. Epub 2022 Jan 10.
PMID: 35007127DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maureen M O'Brien
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 29, 2016
First Posted
December 5, 2016
Study Start
June 19, 2017
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
May 4, 2026
Record last verified: 2026-04