GD2-CAR T Cells for Pediatric Brain Tumours

Launched by BAMBINO GESÙ HOSPITAL AND RESEARCH INSTITUTE · Mar 18, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called iC9-GD2-CAR T cells for children and young adults with certain types of brain tumors that have not responded to previous treatments. The main goal is to see if this treatment is safe and effective. The iC9-GD2-CAR T cells are designed to target a specific marker (GD2) found on some cancer cells, and they include a special “safety switch” that helps protect the patient if there are serious side effects.

To be eligible for this study, participants must be between 6 months and 30 years old and have measurable disease on MRI scans. They should also have recovered from any severe side effects of previous treatments. Participants will need to have certain devices implanted for the study, and parents or guardians must provide consent. During the trial, patients can expect to undergo monitoring and receive the CAR T-cell therapy, with the hope of improving their condition. It’s important to note that there are specific health criteria that must be met, so not all patients will qualify. If interested, families should discuss this opportunity with their healthcare provider for more information.

Gender

ALL

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)