Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

NCT ID: NCT03913559

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-14
• Study Completion Date: 2031-12-31

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).

Detailed Description

The drug will be administered intravenously on days 1, 8, and 15 of each 28-day cycle. Patients who do not meet the definition of treatment failure after the first cycle may receive up to five additional cycles of therapy. .

After completion of study treatment, patients are followed for 1 year.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inotuzumab ozogamicin

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

Group Type: EXPERIMENTAL

Inotuzumab ozogamicin

Intervention Type: DRUG

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.

Methotrexate

Intervention Type: DRUG

Intrathecal (IT) therapy

Hydrocortisone

Intervention Type: DRUG

Intrathecal (IT) therapy

Cytarabine

Intervention Type: DRUG

Intrathecal (IT) therapy

Diphenhydramine

Intervention Type: DRUG

1 mg/kg (max 50 mg) IV

Acetaminophen

Intervention Type: DRUG

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

Methylprednisolone

Intervention Type: DRUG

1 mg/kg IV x 1

Interventions

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.

Intervention Type: DRUG

Methotrexate

Intrathecal (IT) therapy

Intervention Type: DRUG

Hydrocortisone

Intrathecal (IT) therapy

Intervention Type: DRUG

Cytarabine

Intrathecal (IT) therapy

Intervention Type: DRUG

Diphenhydramine

1 mg/kg (max 50 mg) IV

Intervention Type: DRUG

Acetaminophen

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

Intervention Type: DRUG

Methylprednisolone

1 mg/kg IV x 1

Intervention Type: DRUG

Other Intervention Names

Besponsa; CMC-544; Trexall®; Cortisol; Ara-C; Benadryl; Tylenol; Solu-Medrol

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.
• Patient with concurrent severe and/or uncontrolled medical conditions that, in the opinion of the investigator, may impair participation in the study or the evaluation of safety and/or efficacy.
• Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen-positive) or C (defined as hepatitis C antibody-positive).
• Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment).
• Male or female participant of reproductive potential must agree to use appropriate methods of contraception for the duration of study treatment and for at least 30 days after last dose of protocol treatment.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sima Jeha, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

Rady Children's Hospital San Diego

San Diego, California, United States

Site Status: RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sima Jeha, MD

Role: CONTACT

referralinfo@stjude.org

866-278-5833

Facility Contacts

Deborah Schiff, MD

Role: primary

dschiff@rchsd.org

858-966-5811

Sima Jeha, MD

Role: primary

referralinfo@stjude.org

866-278-5833

References

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.

Reference Type: DERIVED

PMID: 35622074 (View on PubMed)

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St.Jude

Other Identifiers

NCI-2019-01062

Identifier Type: REGISTRY

Identifier Source: secondary_id

INOMRD

Identifier Type: -

Identifier Source: org_study_id