Recurrent B Acute Lymphoblastic LeukemiaPhase 2NCT02981628
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
A Phase 2 study testing Asparaginase Erwinia chrysanthemi, Biospecimen Collection and Bone Marrow Aspiration and Biopsy in people with Recurrent B Acute Lymphoblastic Leukemia and Recurrent B Lymphoblastic Lymphoma, run by Children's Oncology Group at 157 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia
- What is being tested?
- Asparaginase Erwinia chrysanthemi, Biospecimen Collection and Bone Marrow Aspiration and Biopsy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 157 sitesin 2 countries
- Study dates
- 19 Jun 2017to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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)
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
- 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.
- Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
- 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:
- 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
- 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
- 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
- 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
- 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
- Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
- Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Who cannot join
- Patients with any prior history of SOS irrespective of severity
- Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
- Patients who have been previously treated with inotuzumab ozogamicin
- Patients who have previously received HSCT (Cohort 2 only)
- Patients with Down syndrome (Cohort 2 only)
- History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
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- Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
- Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
- Patients who are currently receiving another investigational drug
- Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
- Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
- Patients who are currently receiving or plan to receive corticosteroids except as described below
- Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
- Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
- Patients who have an active uncontrolled infection defined as:
- Positive bacterial blood culture within 48 hours of study enrollment;
- Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
- A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
- Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
- 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, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
- There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
- Female 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 their study participation and for 8 months after the last dose of inotuzumab ozogamicin
- Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
- Lactating females are not eligible unless they agree not to breastfeed their infants
Trial locations and contacts
157 sites in 2 countries.
157 sites in 2 countries
United States156 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Providence Alaska Medical Center
Anchorage, Alaska, 99508
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Tufts Children's Hospital
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Maimonides Medical Center
Brooklyn, New York, 11219
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Missouri Children's Hospital
Columbia, Missouri, 65212
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Kaiser Permanente Downey Medical Center
Downey, California, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Michigan State University
East Lansing, Michigan, 48823
El Paso Children's Hospital
El Paso, Texas, 79905
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
East Carolina University
Greenville, North Carolina, 27834
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Loma Linda University Medical Center
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Norton Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Valley Children's Hospital
Madera, California, 93636
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Banner Children's at Desert
Mesa, Arizona, 85202
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Nemours Children's Hospital
Orlando, Florida, 32827
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Renown Regional Medical Center
Reno, Nevada, 89502
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Corewell Health Children's
Royal Oak, Michigan, 48073
Sutter Medical Center Sacramento
Sacramento, California, 95816
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Memorial Health University Medical Center
Savannah, Georgia, 31404
Maine Children's Cancer Program
Scarborough, Maine, 04074
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Stony Brook University Medical Center
Stony Brook, New York, 11794
State University of New York Upstate Medical University
Syracuse, New York, 13210
Tampa General Hospital
Tampa, Florida, 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Medical Center
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
About this study
Official title: 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)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the morphologic response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin in children with relapsed or refractory CD22+ B acute lymphoblastic leukemia (B-ALL). (Cohort 1)
SECONDARY OBJECTIVES:
- To determine the CR/CRi rate following 2 cycles of inotuzumab ozogamicin therapy. (Cohort 1) II. To determine the safety of single agent inotuzumab ozogamicin administered at the adult recommended phase 2 dose (RP2D) to pediatric patients with relapsed or refractory CD22+ B-ALL. (Cohort 1) III. To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients. (Cohorts 1 and 2) IV. To determine the incidence, severity, and outcomes of sinusoidal obstruction syndrome (SOS) of the liver in patients during inotuzumab ozogamicin therapy and following subsequent treatment, including myeloablative hematopoietic stem cell transplantation (HSCT). (Cohorts 1 and 2) V. To estimate the 3-year event-free survival (EFS), 3-year overall survival (OS), and among responders, duration of CR/CRi for pediatric patients with relapsed or refractory B-ALL treated with inotuzumab ozogamicin. (Cohort 1) VI. To describe inotuzumab ozogamicin pharmacokinetics and immunogenicity in pediatric patients in the presence of overt leukemia and in remission. (Cohort 1) VII. To determine the safe and tolerable dose of inotuzumab ozogamicin in combination with the augmented modified Berlin-Frankfurt-Munster (mBFM) consolidation chemotherapy backbone. (Cohort 2)
EXPLORATORY OBJECTIVES:
- To describe the levels of leukemic blast CD22 surface expression and site density, and to explore the correlation with cytogenetics and clinical outcomes after treatment with inotuzumab ozogamicin. (Cohorts 1 and 2) II. To explore potential mechanisms of resistance to inotuzumab ozogamicin therapy including CD22 splice variants and intracellular signaling pathways. (Cohorts 1 and 2) III. To explore the impact of inotuzumab ozogamicin on humoral immune function and peripheral B cell populations. (Cohorts 1 and 2) IV. To describe the level of MRD by next-generation high-throughput sequencing (HTS) techniques which may detect low level leukemic blast populations that have altered CD22 expression. (Cohorts 1 and 2) V. To prospectively explore candidate SOS biomarkers including the endothelial marker of inflammation Angiopoietin 2 (Ang2) and the hepatic specific complement marker L-ficolin. (Cohorts 1 and 2) VI. To explore the use of prophylactic ursodeoxycholic acid (UDCA) to prevent hepatic damage and SOS during inotuzumab ozogamicin therapy and subsequent HSCT. (Cohorts 1 and 2) VII. To describe the interaction between inotuzumab ozogamicin and chimeric antigen receptor (CAR) T cell therapy before or after treatment with inotuzumab ozogamicin. (Cohorts 1 and 2) VIII. To estimate the CR/CRi rate following one cycle of inotuzumab ozogamicin plus augmented mBFM consolidation chemotherapy (first 42 days) and following 2 cycles within the confines of a pilot study. (Cohort 2)
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive inotuzumab ozogamicin intravenously (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: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, and 8. Patients also receive cyclophosphamide IV over 30-60 on day 1; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4 and 8-11; leucovorin calcium orally (PO) or IV on days 2, 9, 16, 23 and 37 of cycle 1 and days 9 and 37 of cycle 2; pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase intramuscularly (IM) on day 15; and vincristine IV on days 15 and 22. Patients receive methotrexate intrathecally (IT) on days 1, 8 and 36 of cycle 1 and day 36 of cycle 2 for CNS 1 patients, days 1, 8, 15, 22 and 36 of cycle 1, and day 36 of cycle 2 for CNS 2 patients. CNS 3 patients receive methotrexate intrathecal triple therapy (ITT) IT on days 1, 8, 15, 22 and 36 of cycle 1 and days 8 and 36 of cycle 2. There are 3 dose levels. If excessive toxicity is observed at dose level 1, the dosing of inotuzumab ozogamicin will be decreased for dose level -1 and 6-mercaptopurine omitted. If excessive toxicity is observed at this dose, then for dose level -2, the dosing of inotuzumab ozogamicin and cyclophosphamide will be decreased. Treatment repeats every 42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration or biopsy, lumbar puncture, and blood sample collection throughout the trial. Patients also undergo imaging on screening and on study.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then yearly for 4 years.
- Conditions
- Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
- Being tested
- Asparaginase Erwinia chrysanthemi, Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Calaspargase Pegol, Cyclophosphamide
- Medical subject headings
- Burkitt Lymphoma, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asparaginase Erwinia chrysanthemiDrug
Also called Asparaginase Erwinia chrysanthemi (Recombinant)-rywn, Asparaginase Erwinia chrysanthemi, Recombinant-rywn, Asparaginase Erwinia chrysanthemi-rywn, Crisantaspase
Given Asparaginase Erwinia chrysanthemi
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo a bone marrow aspiration and biopsy
Calaspargase PegolDrug
Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IV or SC
Diagnostic Imaging TestingProcedure or surgery
Also called Diagnostic Imaging, Medical Imaging
Undergo imaging
Inotuzumab OzogamicinBiological
Also called Besponsa, CMC 544, CMC-544, CMC544
Given IV
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given PO or IV
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Undergo lumbar puncture
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase
Given IV or IM
VincristineDrug
Also called LCR, Leurocristine, VCR, Vincrystine
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (inotuzumab ozogamicin) | Experimental | Patients 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) Receives: Biological: Inotuzumab Ozogamicin |
| Cohort II (inotuzumab ozogamicin, mBFM chemotherapy) | Experimental | See Detailed Description Receives: Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Procedure: Diagnostic Imaging Testing; Biological: Inotuzumab Ozogamicin; Drug: Leucovorin Calcium; Procedure: Lumbar Puncture; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 days
Secondary outcomes (10)
Morphologic response (CR + CRi) following 2 cycles of inotuzumab ozogamicin therapy (Cohort1)
The response rate will be estimated using the proportion of eligible/evaluable patients with CR/CRi response.
Measured: Up to 56 days
Incidence of dose-limiting toxicities at recommended phase II dose (RP2D) (Cohort 1)
Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.
Measured: During Cycle 1, up to 28 days
Level of minimal residual disease (MRD) assessed in bone marrow by flow cytometry (Cohort 1 and 2)
MRD negativity rates (< 0.01% detectable leukemia cells) will be estimated.
Measured: Up to 2 cycles
Incidence of adverse events of sinusoidal obstruction syndrome (SOS) of liver (Cohort 1 and 2)
Evaluated according to NCI CTCAE version 5.0. The incidence of SOS of the liver in patients during inotuzumab ozogamicin therapy and following subsequent treatment including myeloablative hematopoietic cell transplantation (HSCT) will be described.
Measured: Up to 1 year from last dose of Inotuzumab ozogamicin
Event free survival (EFS) (Cohort 1)
The EFS rate will be estimated using Kaplan Meier approach.
Measured: 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
Overall survival (OS) (Cohort 1)
The OS rate will be estimated using Kaplan Meier approach.
Measured: From the time from study entry to death or date of last follow-up, assessed up to 3 years
Duration of CR, CRi (Cohort 1)
Among responding patients, three-year complete continuous response will also be estimated using duration of CR/CRi for the overall responding group and stratified by whether or not the patients proceed to HSCT.
Measured: Up to 3 years
Pharmacokinetic (PK) parameters, i.e., inotuzumab ozogamicin trough levels (Cohort 1)
Inotuzumab ozogamicin trough levels (ng/mL) will be determined in serum by validated, high sensitivity liquid chromatography-mass spectrometry (LCMS) assays. Descriptive summary statistics will be provided for the trough levels at scheduled visits for Cycles 1 and 2.
Measured: Cycles 1 and 2 (each cycle is 28 days)
Immunogenicity (Cohort 1)
Enhanced chemiluminescence (ECL) and cell-based assays will be used to detect anti-drug antibodies and neutralizing antibodies to inotuzumab ozogamicin in serum. Inotuzumab ozogamicin trough levels will be compared between patients with and without antibodies.
Measured: Cycles 1 and 2
Incidence of dose-limiting toxicities at the selected dose level of inotuzumab ozogamicin in combination with the augmented modified Berlin-Frankfurt-Munster (mBFM) consolidation chemotherapy (Cohort 2)
Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.
Measured: Up to cycle 1 (each cycle is 42 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start19 Jun 2017
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Recurrent B Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Maureen M O'Brien, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981628
- Sponsor's protocol ID
- AALL1621
- Other IDs
- NCI-2016-01494, AALL1621, AALL1621, U10CA180886
- Status last verified
- Sep 2026
- First submitted
- 29 Nov 2016
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.
PubMed 41671463Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
PubMed 35622074O'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.
PubMed 35007127