CAR T-cell therapy for pediatric brain tumors

Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T Cells in Pediatric and Young Adult Patients Affected by Relapsed/Refractory Central Nervous System Tumors

This study is testing a new CAR T-cell therapy for kids and young adults with tough brain tumors to see if it can safely help them when other treatments have failed.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 6 Months to 30 Years
• Sex: All
• Sponsor: Bambino Gesù Hospital and Research Institute (other)
• Drugs / interventions: chemotherapy, Radiation, CAR T
• Locations: 1 site (Roma, Italy)
• Trial ID: NCT05298995 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of iC9-GD2-CAR T-cells, a third generation CAR T-cell treatment targeting GD2, in pediatric and young adult patients with relapsed or refractory malignant central nervous system tumors. It involves a Phase I dose escalation approach, where patients will receive intravenous injections of autologous iC9-GD2-CAR T-cells after undergoing leukapheresis. The study is designed to sequentially enroll patients based on the risk associated with their tumor type and location, ensuring safety by starting with lower-risk patients. A suicide gene safety switch is included to manage potential toxicities effectively.

Who should consider this trial

Good fit: Ideal candidates are pediatric or young adult patients aged 6 months to 30 years with relapsed or refractory malignant CNS tumors.

Not a fit: Patients with stable disease or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children and young adults with difficult-to-treat brain tumors.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results in treating various cancers, suggesting potential success for this novel approach in pediatric brain tumors.

Eligibility criteria

Inclusion Criteria:

1. Imaging assessments performed within 14 days of start of treatment
2. Age: 6months-30years
3. Measurable or evaluable disease on at least 2 dimensions on MRI at the time of treatment enrollment
4. Karnofsky/Lansky≥60
5. Recoverfromthetoxiceffectsofpreviousradiationandchemotherapies:grade4and or 3 non-hematologic toxicities must have resolved to grade ≤ 2; in presence of chronic complications (i.e. treatment-associated thrombocytopenia), patient must be clinically stable, according to the opinion of the treating physicians, and meet all other eligibility criteria
6. Positioning of an implantable intraventricular access device (CodmanHolterRickham reservoir, Integra LifeSciences, NJ, U.S.A) and a microdialysis probe (71 high cutoff microdialysis bolt catheter, M Dialysis AB, Stockholm Sweden)
7. Written and signed informed consent from patients, parents or legal guardians. For subjects \< 18 year-old their legal guardian must give informed consent. In addition, pediatric subjects will be included in age-appropriate discussion and written informed assent will be obtained for those greater than or equal to 7 years of age, when appropriate
8. Patients of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
9. Females of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus

Exclusion Criteria:

1. Pregnant or lactating women
2. Severe,uncontrolledactiveinfections
3. HIV or active HCV and/or HBV infection
4. Rapidly progressive disease with life expectancy \< 6 weeks
5. Historyofgrade3or4hypersensitivitytomurineprotein-containingproducts
6. Hepatic function: inadequate liver function defined as total bilirubin \> 4x upper limit of normal (ULN) or transaminase (ALT and AST) \> 6 x ULN based on age and laboratory specific normal ranges
7. Renal function: serum creatinine \> 3x ULN for age
8. Blood oxygen saturation \< 90%
9. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO
10. Marrow function: absolute neutrophils count (ANC) lower than 500/mm3 and/or platelets lower than 20.000 (not reached by transfusion)
11. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the principal investigator (PI) would pose an unacceptable risk to the subject. 12.Concurrent or recent prior therapies, before infusion:

    1. If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to infusion. Recent or current use of inhaled/topical/non- absorbable steroids is not exclusionary. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis
    2. Systemic chemotherapy in the 3 weeks preceding infusion
    3. Immunosuppressive agents less than or equal to 30 days
    4. Radiation therapy must have been completed at least 6 weeks prior to enrollment
    5. Otheranti-neoplasticinvestigationalagentscurrentlyorwithin30dayspriorto start of protocol therapy

13.Patient-derived GD2-CART01 production failure: vitality \<80%, CD3+ cells \<80%, CD3+ CAR+ cells \<20%, CD3+ CAR+ antitumor activity \<60% in functional co-culture assay at an Effector: Target ratio 1:1, viable CAR+ cells upon AP1903 exposition \>20%, RCR positivity, Vector Copy Number \>10, non-sterility, endotoxin contamination (\> 1 EU/ml)

Where this trial is running

Roma, Italy

• Ospedale Pediatrico Bambino Gesù — Roma, Italy, Italy (RECRUITING)

Study contacts

• Study coordinator: Francesca Del Bufalo, MD

Conditions: Brain Tumor, Pediatric, Medulloblastoma, Childhood, Embryonal Tumor, High Grade Glioma, Diffuse Midline Glioma, Diffuse Intrinsic Pontine Glioma, Brain Tumor Adult, Brain tumors