NCT03913559

Brief Summary

This trial is a limited multi-center, Phase II study to evaluate inotuzumab ozogamicin (Besponsa) in pediatric patients with MRD positive CD22-positive B-lymphoblastic leukemia (B-ALL). Some patients with newly diagnosed ALL maintain low levels of MRD, despite achieving complete remission with less than 5% blasts in the bone marrow. Others experience re-emergence of low level MRD or increasing levels of MRD on therapy or post-transplant. New approaches are needed to achieve undetectable MRD in these high-risk patients. Inotuzumab ozogamicin is an antibody-drug conjugate composed of a humanized IgG subtype 4 monoclonal CD22-targeted antibody linked to calicheamicin, a potent anti-tumor antibiotic. CD22 is expressed in more than 90% of patients with B-cell ALL, making it an attractive target in this patient population. Inotuzumab ozogamicin has demonstrated exceptional activity in adults with relapsed or refractory B-ALL. Primary Objective

  • Assess the efficacy of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL with 0.1 - 4.99% blasts in bone marrow. Secondary Objectives
  • Study the safety of inotuzumab ozogamicin when used in patients with MRD - positive CD22+ B-ALL with \< 5 % blasts in bone marrow.
  • Estimate the incidence, severity, and outcome of hepatotoxicity and sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in patients during inotuzumab ozogamicin and following subsequent treatment, including hematopoietic stem cell transplant (HSCT).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2019

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
terminated

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

April 9, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 12, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

May 14, 2019

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 15, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 15, 2025

Completed
Last Updated

February 12, 2026

Status Verified

February 1, 2026

Enrollment Period

6.3 years

First QC Date

April 9, 2019

Last Update Submit

February 10, 2026

Conditions

Keywords

B-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (4)

  • Treatment response Cycle1 - count

    Number of patients that reach MRD negative at the end of cycle 1

    At the end of cycle 1 (each cycle is 28 days)

  • Treatment Response Cycle 1 - percentage

    Percentage of patients that reach MRD negative at the end of cycle 1

    At the end of cycle 1 (each cycle is 28 days)

  • Treatment Response Cycle 2 - count

    Number of patients that reach MRD negative at the end of cycle 2

    At the end of cycle 2 (each cycle is 28 days)

  • Treatment Response Cycle 2 - percentage

    Percentage of patients that reach MRD negative at the end of cycle 2

    At the end of cycle 2 (each cycle is 28 days)

Secondary Outcomes (4)

  • Occurrence of death - count

    up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant

  • Occurrence of death - percentage

    up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant

  • Occurrence of Veno-occlusive disease (VOD) - count

    up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant

  • Occurrence of Veno-occlusive disease (VOD) - percentage

    up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant

Study Arms (1)

Inotuzumab ozogamicin

EXPERIMENTAL

Experimental:Inotuzumab Ozogamicin (InO) Patients with B cell acute lymphoblastic leukemia (B-ALL) that is showing early signs of relapsing (coming back) or is not responding to treatment (refractory). Interventions:methotrexate, hydrocortisone and cytarabine into the central nervous system (called triple intrathecal chemotherapy or IT chemotherapy) during this study. Premedication: diphenhydramine, acetaminophen and methylprednisolone

Drug: Inotuzumab ozogamicinDrug: MethotrexateDrug: HydrocortisoneDrug: CytarabineDrug: DiphenhydramineDrug: AcetaminophenDrug: Methylprednisolone

Interventions

Intrathecal (IT) therapy

Also known as: Trexall®
Inotuzumab ozogamicin

Intrathecal (IT) therapy

Also known as: Cortisol
Inotuzumab ozogamicin

Intrathecal (IT) therapy

Also known as: Ara-C
Inotuzumab ozogamicin

1 mg/kg (max 50 mg) IV

Also known as: Benadryl
Inotuzumab ozogamicin

10 mg/kg (max 650 mg) PO x 1

Also known as: Tylenol
Inotuzumab ozogamicin

1 mg/kg IV x 1

Also known as: Solu-Medrol
Inotuzumab ozogamicin

dose: 0.5 mg/m2 IV over 60 minutes, days: 1, 8 and 15 every 4 weeks (28 days per cycle) for up to 6 cycles.

Also known as: Besponsa, CMC-544
Inotuzumab ozogamicin

Eligibility Criteria

AgeUp to 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Age
  • Participants must be \< 22 years of age.
  • Diagnosis
  • Participants must have B-ALL with persistent or rising MRD between 0.1 and 4.99% without extramedullary disease following at least two prior induction attempts, relapse or after hematopoietic stem cell transplant
  • Leukemia blasts demonstrating surface expression of CD22
  • Performance Level
  • Karnofsky or Lansky performance score ≥ 50% (corresponding to ECOG Score of ≥ 2). The Lansky performance score should be used for participants \< 16 years and the Karnofsky performance score for participants ≥ 16 years.
  • Prior Therapy

You may not qualify if:

  • At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids.
  • At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
  • At least 42 days must have elapsed since CAR-T cell therapy.
  • Participant has received ≤ 1 prior bone marrow transplant.
  • At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for ≥ 2 weeks, if applicable with no evidence of active GVHD.
  • At least 2 weeks must have elapsed since local 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 TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
  • Organ Function Requirements
  • Adequate renal function defined as glomerular filtration rate ≥ 60 cc/min/1.73m2 or serum creatinine based on age as follows:
  • Age: \<6 months; maximum serum creatinine (mg/dL): 0.4 (male, female); Age: 6 months to \<1 year; maximum serum creatinine (mg/dL): 0.5 (male, female); Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to \<10 years; maximum serum creatinine (mg/ dL): 1 (male, female); Age: 10 to \<13 years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to \<16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age: ≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
  • Adequate hepatic function defined as:
  • Direct bilirubin ≤ 1.4 mg/dL (if total bilirubin \> 1.4 mg/dL) and
  • AST or ALT ≤ 3 x ULN for age.
  • Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.
  • History of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of any severity.
  • Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecal therapy.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaBurkitt Lymphoma

Interventions

Inotuzumab OzogamicinMethotrexateHydrocortisoneCytarabineDiphenhydramineAcetaminophenMethylprednisoloneMethylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

CalicheamicinsAminoglycosidesGlycosidesCarbohydratesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds11-HydroxycorticosteroidsHydroxycorticosteroidsAdrenal Cortex HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists17-HydroxycorticosteroidsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesEthylaminesAminesOrganic ChemicalsBenzhydryl CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsAcetanilidesAnilidesAmidesAniline CompoundsPrednisolonePregnadienetriolsPregnadienes

Study Officials

  • Sima Jeha, MD

    St. Jude Children's Research Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 9, 2019

First Posted

April 12, 2019

Study Start

May 14, 2019

Primary Completion

September 15, 2025

Study Completion

September 15, 2025

Last Updated

February 12, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Data will be made available at the time of article publication.
Access Criteria
Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations