Using Inotuzumab Ozogamicin for Children with High-Risk Leukemia

Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

This study tests if a new treatment called inotuzumab ozogamicin can help children with a tough type of leukemia who still have cancer cells after other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: blinatumomab, CAR-T, chemotherapy, inotuzumab
• Locations: 2 sites (San Diego, California and 1 other locations)
• Trial ID: NCT03913559 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the efficacy of inotuzumab ozogamicin in pediatric patients with minimal residual disease (MRD) positive CD22-positive B-lymphoblastic leukemia (B-ALL). The study aims to treat children who have persistent or rising MRD levels despite previous treatment attempts. Inotuzumab ozogamicin, an antibody-drug conjugate, targets CD22, which is commonly expressed in B-ALL, and is administered intravenously over a series of cycles. Patients will be monitored for one year following treatment to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates are children under 22 years old with B-ALL and persistent or rising MRD levels after prior treatments.

Not a fit: Patients with extramedullary disease or those who do not express CD22 on their leukemia cells may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could lead to improved outcomes for children with high-risk leukemia by achieving undetectable MRD levels.

How similar studies have performed: Previous studies have shown promising results with inotuzumab ozogamicin in adult populations, indicating potential for success in pediatric cases.

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

* Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria prior to entering this study.
* 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 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab. Patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to Grade 2 or lower as outlined in the inclusion/exclusion criteria.
* 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%.

Exclusion Criteria:

* 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.

Where this trial is running

San Diego, California and 1 other locations

• Rady Children's Hospital San Diego — San Diego, California, United States (Recruiting)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Sima Jeha, MD — St. Jude Children's Research Hospital
• Study coordinator: Sima Jeha, MD

Conditions Acute Lymphoblastic Leukemia; B-cell Acute Lymphoblastic Leukemia