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

NCT06221553 | Recruiting Phase 1 DMC

• 2 other identifiers: LV-B7H3IL7-CART-DPG-P1-2023Chulalongkorn University
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

DIPG Brain Tumor; Diffuse Intrinsic Pontine Glioma

Keywords

CAR T cell; DIPG; B7H3; IL-7 receptor alpha; Chimeric antigen receptor T cell; Adoptive cellular therapy

Outcome Measures

Primary Outcomes (1)

• Safety of B7H3-IL7Ra CAR T cells infusion in diffuse intrinsic pontine glioma (DIPE) patients.

  The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0

  Up to 28 days after B7H3-IL7Ra CAR-T cell infusion

Secondary Outcomes (1)

• The overall response rate of diffuse intrinsic pontine glioma (DIPE)

  3, 6, and 12 months after B7H3-IL7Ra CAR-T cell infusion

Other Outcomes (2)

• The persistence and distribution of B7H3-IL7Ra CAR T cells in the CSF and peripheral blood

  14 days, 28 days, 42 days 3 months, 6 months, and 12 months after B7H3-IL7Ra CAR-T cell infusion

• Serum cytokine level measurement

  1 day, 14 days, 28 days and 42 days after B7H3-IL7Ra CAR-T cell infusion.

Study Arms (1)

Locoregional delivery of B7H3/IL-7Ra CAR T cell in DIPG

EXPERIMENTAL

Patients with DIPG for whom CAR T cells will be delivered into the ventricular system Interventions: Biological: Autologous B7H3-specific chimeric antigen receptor (CAR) T cell with additional of IL-7Ra signaling domain Dose level: 1x10e7 CAR T cell, 3x10e7 CAR T cell, 10x10e7 CAR T cell

Biological: B7H3 specific CAR T cell with IL-7Ra signaling domain

Interventions

B7H3 specific CAR T cell with IL-7Ra signaling domain BIOLOGICAL

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

Locoregional delivery of B7H3/IL-7Ra CAR T cell in DIPG

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chulalongkorn University: lead
• King Chulalongkorn Memorial Hospital: collaborator

Study Sites (1)

King Chulalongkorn Memorial Hospital

Bangkok, Pathumwan, 10330, Thailand

RECRUITING

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Piti Techavichit, MD

  Chulalongkorn University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Piti Techavichit, MD

CONTACT

6622564900; piti.t@chula.ac.th

Koramit Suppipat, MD

CONTACT

6622564900; koramit.s@chula.ac.th

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation study

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 24, 2024
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)