RecruitingPhase 1NCT06221553

Safety and Efficacy of Loco-regional B7H3 IL-7Ra CAR T Cell in DIPG

Safety and Efficacy of Intraventricular Infusion of B7H3 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell in Diffuse Intrinsic Pontine Glioma

Sponsor

Chulalongkorn University

Enrollment

9 participants

Start Date

Mar 1, 2024

Study Type

INTERVENTIONAL

Conditions

Diffuse Intrinsic Pontine Glioma DIPG Brain Tumor

Summary

A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cell with IL-7Ra signal targeting B7H3 in children with diffuse intrinsic pontine glioma (DIPG) patients after complete standard treatments.

Eligibility

Min Age: 1 YearMax Age: 18 Years

Inclusion Criteria10

Participants must have diffuse intrinsic pontine glioma at any timepoint following completion of standard radiotherapy
Age 1-18 years
Sex: Male or female
CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy
Performance status: Lansky or Karnofsky score \>= 60
Life expectancy \>= 8 weeks
Normal organ function:
AST (SGOT) \< 5 times the upper limit of normal (ULN) 7.2 ALT (SGPT) \< 5 times the upper limit of normal (ULN) 7.3 Total bilirubin \< 3 times the upper limit of normal (ULN) 7.4 Creatinine \< 5 times the upper limit of normal (ULN) 7.5 SpO2 room air \>=90%
Prior therapy wash-out before planned leukapheresis 8.1 \>= 7 days post last chemotherapy/biologic therapy administration 8.2 3 half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy 8.3 At least 30 days from most recent cellular infusion 8.4 All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum dexamethasone dose of 2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed
Participants and/or legal guardians must have the ability to understand and willingness to sign a written informed consent and/or assent document

Exclusion Criteria8

Presence of \>= grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention
Presence of primary immunodeficiency or bone marrow failure syndrome
Presence of clinical and/or radiographic evidence of impending herniation of CNS
Presence of \> Grade 3 dysphagia
History of active malignancy other than nonmelanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast).
Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant or breastfeeding women were excluded from this study because CAR-T-cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion.
Serologic status reflecting active HIV, hepatitis B or C infection. Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.

Interventions

BIOLOGICALB7H3 specific CAR T cell with IL-7Ra signaling domain

Autologous T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) with additional of IL-7 receptor alpha signalingdomain given via indwelling central nervous system (CNS) catheter